Lupus Homeopathic Remedies

Natural Lupus Treatment System

Natural Lupus Treatment by Dr. Gary Levin is an easy-to-understand e-book and comes together with a quick start guide and the audio version of the system. With the method that Lupus patients will learn in Natural Lupus Treatment, they will not need pills, injections, and other risky methods to take their lupus away. Patients just need to follow the steps laid out in this system and they can cure their lupus and enjoy a normal life again. Actually there is no cure yet discovered for lupus, however, you will find methods to control and manage its signs and symptoms. The aim of the treatments of lupus generally would be to let the patient experience more comfort and lesser pain. More here...

Proven Lupus Treatment By Dr Gary Levin Overview


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The management of skin conditions in general practice

One great advantage of general practice is that there is continuity of care and the family doctor has a much more complete overall picture of the patient, their family and social circumstances than can be acquired in a hospital consultation. Increasingly dressings and other treatments are being used by practice nurses in conjunction with the dermatology liaison nurse when necessary. This applies to inflammatory skin conditions such as psoriasis and eczema as well as leg ulcers, but also to conditions such as Darier's disease, dermatitis herpetiformis, and lupus erythematosus where regular supervision and blood tests may be required. There is no reason why continuing treatment with drugs such as ciclosporin and methotrexate cannot be carried out in general practice once the diagnosis and treatment regime have been established. Regular blood tests are mandatory when these drugs are being used.

Cells and Immunoglobulins

Probably the best example for an immunoglobulin-mediated disease is pemphigus vugaris. In patients, this disease is associated with little inflammation and seems to be directly mediated by the binding of autoreactive immunoglobulins to the desmogleins that guarantee the adherence between kerati-nocytes (Amagai et al. 1991). Indeed, transfer of patient sera and monoclonal antibodies directed against desmoglein 3 into the skin of new-born mice can directly induce acanthosis (Rock et al. 1989). This critical role for a direct binding of immunoglobulins to desmoglein structures is further supported by the observation that in patients with pemphigus vugaris the disease activity correlates closely with the serum levels of the autoantibodies (Hertl 2000). Such a close association is unusual for other autoimmune diseases, including lupus erythematosus or bullous pemphigoid. For comparisons, bullous pemphigoid is of special interest. It is also an immunoglobulin mediated bullous skin disease....

Mycobacterial disease

The clinical presentation of infections due to mycobacteria, a specific group of organisms that includes the causes of tuberculosis and leprosy, reflects the success of the host's response in eradicating organisms. There are clear differences, for instance, between disseminated miliary tuberculosis and lupus vulgaris or, for example, tuberculoid and lepromatous leprosy. These are discussed in chapter 23. As these infections are not common only lupus vulgaris and non-tuberculous or atypical mycobacterial infection are described.

Risk Factors that Effect the Prognosis of SLE

Rzany et al. (1996) showed in a study of 282 SLE patients, that younger (0-19 years) or older (> 40 years) age at baseline (entry into the study group) is associated with a higher risk of developing hypercreatinemia (RR 5.13 95 CI 1.4-18.8 and 4.09 2.1-8.2, respectively). Other factors that increase the risk of renal damage are involvement of other organ systems, namely serositis (RR 2.17 1.1-4.3) and as a trend neurologic lupus (RR 1.96 1.0-4.0), immunosuppressive treatment (excluding prednisone) at baseline (RR 2.39 1.0-5.6) and the presence of anti-dsDNA antibodies (RR 1.17 1.0-1.4). Longer duration of the disease at baseline led to a 25 (10 -50 ) increase in risk for every five years.

Clinical Appearance Classification

Pictures Ulcers From Lupus

Acute cutaneous lupus erythematosus (ACLE) Localized Subacute cutaneous lupus erythematosus (SCLE) Annular Papulosquamous Chronic cutaneous lupus erythematosus (CCLE) Discoid (DLE) Localized (above neck) Generalized (above and below neck) follicular Hypertrophic DLE Mucosal LE Lupus panniculitis Lupus profundus (Panniculitis and DLE) Lupus tumidus Chilblain lupus Papulous mucinosis form is chronic discoid lupus erythematosus (CDLE or DLE). It is character zed by persistent, sharply demarcated, elevated erythematous plaques with adherent scales which may rarely ulcerate (Fig. 1A). Early stages are characterized by erythema and hyperpigmentation. The characteristic painful sensation upon touching is caused by follicular plugging resulting in the so-called carpet-tack sign. Apart from that, atrophy and scarring can be found in the center of untreated lesions and may result in considerable disfiguration particularly when present in the face (Fig. 1B). A characteristic pitted, acneiform...

Clinical Variants of Pemphigus

Pemphigus Folicaceous Epidermis

Pemphigus erythematosus (Senear Usher) can be considered as a variant of PF which is characterized by sharply demarcated erythematous plaques with scaling. The lesions are primarily localized on the face and the upper trunk (Senear and Usher 1926). A characteristic immunoserological feature is the presence of IgG and C3 deposits along the dermoepidermal membrane similar to lupus erythematosus. About 80 of these patients have serum antinuclear Ab. The precise nature of this disorder and the role that anti-Dsg1 auto-Ab play remains to be elucidated.

Type 2 T Cells and TB Cell Interactions

A large number of autoimmune diseases is immunoglobulin mediated. These 'humoral' diseases can roughly be divided into two major categories. Immu-noglobulins can induce damage through direct binding of their target-antigen. This is the situation in most other bullous autoimmune diseases of the skin, especially pemphigus vulgaris. Alternatively immunoglobulins bind to circulating antigens and cause damage through deposition along basement membranes or in vessels. The former situation is given in the case of lupus (Rubin 1997) the latter at sites of vasculitis.

Etiology and Pathogenesis

The etiology of EBA is unknown, but because the disease features IgG autoantibodies directed against type VII collagen, it is thought that EBA has an autoimmune pathogenesis (Woodley et al. 1984,1988). Another autoimmune bullous skin disease which may exhibit auto-antibodies against type VII collagen is bullous systemic lupus erythematosus (SLE) (Gammon et al. 1985). Both EBA and bullous SLE patients often have a common human leukocyte antigen (HLA) major histocompatibility (MHC) class II cell surface protein, HLA-DR2 (Gammon et al. 1988b). This HLA phenotype has been associated with hyperimmunity which again suggests an autoimmune etiology for EBA.

Definition and Classification

Lupus erythematosus (LE) is a polyclonal T and B lymphocyte autoimmune disease thought to result from a complex interplay of genetic and environmental factors. Clinical expression of LE ranges in continuum from minor cutaneous lesions to life-threatening vital organ dysfunction. Throughout this continuum skin manifestations are variable and common. In 1981 Gilliam and Sontheimer developed a classification system that divides lesions into LE specific and LE non-specific cutaneous disease. LE specific cutaneous disease includes three clinically, immunologically and genetically distinct disorders acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE) and chronic cutaneous LE (CCLE). Histopathological differentiation between especially the first two disorders can be difficult.

Cutaneous Manifestations

Classical DLE is the most common form of CCLE and may be seen in some SCLE patients. DLE lesions are more common on the scalp and face and have more hypopigmentation, hyperpigmentation, scarring, follicular plugging, and adherent scale than SCLE lesions. Induration was the most important clinical feature differentiating DLE from SCLE lesions (David-Bajar et al. 1992). Lupus panniculitis, often reported in association with DLE, has recently been reported in association with SCLE (Morgan & Callen 2001).

Clinical Appearence Classification

Both forms, however, lead to life threatening involvement of internal organs and large areas of the skin and are associated with marked excess mortality. The quality of life is severely reduced and the patients require continous medical support. Institution of regular physical therapy as early as possible to prevent loss of function is mandatory. Patient support groups play an important role in helping these patients to cope with their difficult psychosocial situation. The two major clinical variants are distinguished primarily on the degree and extent of skin involvement. The term overlap syndrome is used when features commonly encountered in other connective tissue diseases are present such as polymyositis or systemic lupus erythematosus.


This drug is used for systemic lupus erythematosus, pemphigus, and bullous pemphigoid. It enables the dosage of systemic steroids to be reduced. The most serious side effect is bone marrow suppression. This may occur quite rapidly, particularly in those with diminished ability to metabolise the drug. This is carried out by thiopurine methyl transferase (TMT). The level of this enzyme should therefore be determined before treatment is started and those at low levels given a lower dosage. Those who inherit high activity may require higher doses. Other side effects include gastrointestinal upset, liver toxicity, and an increased tendency to infection.


Only a lymphocytic infiltrate with fibrosis and ectatic capillaries were seen (Warren and Cockerell 2002). Therefore, biopsies for histopathologic examination should be taken from an early papule, papulovesicle, or a small blister with healthy appearing skin immediately adjacent to it. Typical histological changes are best seen in the vicinity of early blisters (Fig. 5). The initial inflammatory event is variable edema in the papillary dermis with discrete subepider-mal vacuolar alteration and neutrophils along the dermal-epidermal junction. As the lesion develops, neutrophils, to a lesser extent eosinophils, and fibrin accumulate within the dermal papillae and form microabscesses. These become confluent, resulting in a subepidermal blister. It has been demonstrated that split formation occurs within the lamina lucida of the basement membrane zone (Smith et al. 1992). The IgA deposits have been shown to act as a chemoattractant for neutropils (Hendrix et al. 1990). In addition,...


Bullosa acquisita - a pemphigoid like disease. J Am Acad Dermatol 11 820-832 Gammon WR, Woodley DT, Dole KC, Briggaman RA (1985) Evidence that basement membrane zone antibodies in bullous eruption of systemic lupus erythematosus recognize epidermolysis bullosa acquisita autoantigens. J Invest Dermatol 84 472-476 Gammon WR (1988a) Epidermolysis bullosa acquisita. Semin Dermatol 7 218-224 Gammon WR, Heise ER, Burke WA, Fine JD, Woodley DT, Briggaman RA (1988b) Increased frequency of HLA-DR2 in patients with autoantibodies to epidermolysis bullosa acquisita antigen Evidence that the expression of autoimmunity to type VII collagen is HLA class II allele associated. J Invest Dermatol 91 228-232 Gammon WR, Kowalewski C, Chorzelski TP, Kumar V, Briggaman RA, Beutner EH (1990) Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J Am Acad Dermatol 22 664-670 Gammon WR, Briggaman RA (1993)...

Topical steroids

Topical steroids provide effective anti-inflammatory treatment but have the disadvantage of causing atrophy (due to decreased fibrin formation) and telangiectasis. They are readily absorbed by thin skin around the eyes and in flexures. On the face the halogenated steroids produce considerable telangiectasia, so nothing stronger than hydrocortisone should be used (except in lupus erythematosus). They can cause hirsutism and folliculitis or acne. Infection of the skin may be concealed (tinea incognita, for example) or made worse.


A 'positive' LBT shows a 'band' of immunoglobulin and complement reactants at the DEJ of nonlesional skin. The diagnostic and prognostic significance of the LBT is the subject of ongoing debate (Sontheimer and Provost 1996 David-Bajar and Davis 1997). Twenty-six percent of a SCLE cohort had a positive LBT when sun-protected flexor forearm skin was biopsied (Sontheimer and Gilliam 1979). When three or more immunoreactants are present in the LBT of sun-protected skin, the diagnostic specificity for SLE is very high (Velthuis et al. 1992) and a positive LBT correlates with a higher risk of lupus nephritis (Davis and Gilliam 1984). It is unclear if the LBT provides added value to more available, less invasive testing such as serologic assays for double-stranded DNA autoantibodies. The greatest utility of the LBT may be in patients with atypical clinical and laboratory presentations of SLE.


Chronic cutaneous lupus erythematosus (CCLE) comprises different clinical entities with discoid lupus erythematosus (DLE) as the most common form. In contrast to acute cutaneous LE (ACLE) and subacute cutaneous LE (SCLE), lesions are long-lasting for up to decades with occasional spontaneous

Insulin resistant diabetes

Some rare insulin resistant states exist in which hundreds or even thousands of units of insulin may be ineffective. They are often associated with lipodystrophy, hyperlipidaemia, and acanthosis nigricans. Type A insulin resistance is due to genetic defects in the insulin receptor or in the post-receptor pathway. Type B insulin resistance occurs as a result of IgG autoantibodies directed against the insulin receptor it is often associated with other autoimmune disorders such as systemic lupus erythematosis, and it is much commoner in women of African descent. Management of these conditions can be very difficult and specialist texts should be consulted.

Nail plate and soft tissue abnormalities

Lunula Dyschromias

In psoriasis (Figures 4.2-4.4) there is usually a yellow-red margin visible between the pink normal nail and the white separated area. In the 'oil spot' or 'salmon patch' variety, the separation between nail plate and nail bed may start in the middle of the nail this is sometimes surrounded by a yellow margin, inflammatory and eczematous diseases affecting the nail bed. Oil patches have been reported in systemic lupus erythematosus they may be extensive in lectitis purulenta et granulomatosa.

Radiation Therapy Factors

Certain collagen vascular diseases, such as scleroderma and systemic lupus erythematosus, have been associated with an increase in acute skin and subcutaneous toxicity to standard doses of radiotherapy and may be related to inadequate repair of sublethal radiation injury. However, a retrospective review of patients with collagen vascular disease showed that only

Th1 versus Th2 Cytokines in Humoral Autoimmunity

Table 5.5 Cytokine interventions in systemic lupus erythematosus*. Table 5.5 Cytokine interventions in systemic lupus erythematosus*. a) Effect of cytokine modulations in systemic lupus erythematosus. Significant versus mild reductions in the indicated disease parameters are indicated by and j, respectively significant versus mild exacerbations in the indicated disease parameters are indicated by and respectively no significant difference in a disease parameter is indicated by b) BALB c-peptide DWEYSVWLSN-induced lupus in BALB c mice. ND not determined. a) Effect of cytokine modulations in systemic lupus erythematosus. Significant versus mild reductions in the indicated disease parameters are indicated by and j, respectively significant versus mild exacerbations in the indicated disease parameters are indicated by and respectively no significant difference in a disease parameter is indicated by b) BALB c-peptide DWEYSVWLSN-induced lupus in BALB c mice. ND not determined.

Discussion And Conclusion

In patients with systemic lupus erythematosus, in whom CRP is unable to differentiate disease activity, sTNFR-II correlates with clinical disease activity to a remarkable extent, even better than anti-DNA antibodies13'14. Along these lines, our results suggest that elevated levels of this molecule, predict indeed the presence of active disease probably reflecting the neutralization of increased TNF-a bioactivity.

Patients And Methods

The records of 1238 patients with recurrent aphthous stomatitis followed-up at the Multidisciplinary Behcet's Disease Unit at Ankara University Faculty of Medicine during the years 1988-2002 were retrospectively analysed. The patients with systemic diseases known to be associated with oral aphthous lesions such as systemic lupus erythematosus and inflammatory bowel diseases were excluded. At the first visit every patient was evaluated with complete dermatologic examination and ophthalmologic examination. Laboratory tests including complete blood count, serum

Membranoproliferative Glomerulonephritis

The first, known as membranoproliferative (mesangiocapillary) glomerulonephritis type I, is a primary glomerulopathy most common in children and adolescents. The same pattern of injury may be observed during the course of many diseases with chronic antigenemic states these include systemic lupus erythematosus and hepatitis C virus and other infections. In membranoproliferative glomerulonephritis type I, the glomeruli are enlarged and have increased mesangial cellularity and variably increased matrix, resulting in lobular architecture. The capillary walls often are thickened with double contours, an abnormality resulting from peripheral migration and interposition of mesangium (A). Immunofluorescence discloses granular to confluent granular deposits of C3 (B), immunoglobulin G, and immunoglobulin M in the peripheral capillary walls and mesangial regions. The characteristic finding on electron microscopy is in the capillary walls. C, Between the basement membrane and...

The Antiphospholipid Syndrome

The Antiphospholipid Syndrome (APS), also called Hughes syndrome, is a multi-system thrombophilic disorder associated with circulating AABs directed against negatively charged phospholipids (PL) and PL-binding proteins 54, 55 . APS may occur as an isolated disease entity (primary APS) or in combination with another autoimmune disease, especially systemic lupus erythematosus (secondary APS). The clinical features of APS are caused by venous and or arterial thrombosis and or pregnancy morbidity. According to the localization and severity of thrombosis, the clinical picture is extremely variable, and the complications arising from the disease may be minimal to life-threatening. International clinical and laboratory criteria have provided consensus on the typical features of the syndrome 54 . Several manifestations are relatively common in APS patients (deep vein occlusions affecting the lower limbs, stroke, large vessel occlusions, fetal loss, thrombocytopenia, livedo reticularis)....

New diagnostic approaches

To identify the gene expression signatures induced by various pathogens, Chaussabel et al. examined peripheral blood mononuclear cells (PBMCs) obtained from pediatric patients presenting with various illnesses (2005). Specifically, they examined diseases with distinct immunological components such as systemic lupus erythematosus (SLE), influenza A, Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae. They also examined adult patients who received liver transplants with immuno-suppressive therapy or patients who received bone marrow transplants

Now that I have been diagnosed with MS how do I learn to cope with this disease

System lupus erythematosus (SLE) The first step in dealing with MS is acceptance of the diagnosis (i.e., what does the diagnosis mean ). A diagnosis may be easy for the neurologist, but the affected person may not react positively or may even be suspicious about the seeming ease of establishing the diagnosis. Obviously, the confidence in the physician is a prerequisite in accepting the diagnosis. Although physicians other than neurologists may suspect the diagnosis, the diagnosis of MS must be made by a neurologist. It is also assumed that appropriate clinical neurologic examinations and tests such as MRIs of the brain and spinal cord, cerebrospinal fluid (CSF) examination, and certain blood work will be performed and the results reviewed. These tests are usually needed to eliminate other diseases. Illnesses that can sometimes mimic MS, such as syphilis, system lupus erythematosus (SLE) , and vitamin B12 deficiency, must be eliminated from consideration. Occasionally, patients will...

Antimyeloperoxidase Antibodies Mpoancas

Myeloperoxidase (MPO), an enzyme found in the azurophil (primary) granules of neutrophils, is a homodimer with a molecular weight of approximately 140 kDa. MPO-ANCA is the diagnostic marker for MPA in general (sensitivity 60-80 ) as well as a diagnostic marker for immunohistologically negative (pauci-im-mune) focal necrotizing glomerulonephritis, which - when inadequately managed - can transform into extracapillary proliferative, rapidly progressive glomerulonephritis (RPNG). Pauci-immune glomerulonephritis can occur as a component of systemic vasculitis (especially MPA) or as an idiopathic type (without signs of extrarenal vasculitis). MPO-ANCAs are detectable in roughly 65 of patients with this type of glomerulonephritis. Exogenous factors such as medications (mainly hydralazine and propylthiouracil, but also penicillamine, methimazole, allo-purinol, and sulfasalazine) or silica exposure are currently being discussed as potential triggers in some of these cases. MPO-ANCAs are also...

Selected Categories Of Vasculitis

Large vessel vasculitis Giant cell arteritis Takayasu arteritis Medium-sized vessel vasculitis Polyarteritis nodosa Kawasaki disease Small vessel vasculitis ANCA small vessel vasculitis Microscopic polyangiitis Wegener's granulomatosis Churg-Strauss syndrome Immune complex small vessel vasculitis Henoch-Schonlein purpura Cryoglobulinemic vasculitis Lupus vasculitis Serum sickness vasculitis Infection-induced immune complex vasculitis Anti-GBM small vessel vasculitis Goodpasture's syndrome

Anaesthetic problems

Pulmonary involvement may result in a restrictive lung defect.The presence of either acute lupus pneumonitis or pulmonary hypertension is associated with an increased mortality. 2. Thrombotic problems.There is an association between SLE and the antiphospholipid syndrome. Up to 28 of patients with lupus anticoagulant may have 3. Coagulation tests in patients with lupus anticoagulant may show a prolonged PT, APTT or KCCT, or thrombocytopenia and platelet dysfunction. In addition, the patient may be receiving aspirin or low-dose heparin. 5. Antiphospholipid antibodies and the antiphospholipid syndrome.The incidence of lupus anticoagulant and anticardiolipin antibodies is 37 in women with SLE, compared with 5.3 in the normal obstetric population (Kutteh 1997).Their presence can be associated with slow, progressive thrombosis and infarction in the placenta, and a high incidence of fetal loss and maternal morbidity. They can also be associated with a devastating clinical course. One...

Antiphospholipid Antibodies

Lupus anticoagulants and anticardiolipin antibodies were the first such antibodies to be described. The Sapporo laboratory criteria for definite antiphos-pholipid syndrome require both assays to be present on two or more occasions at least six weeks apart 148 . Lupus anticoagulant must be diagnosed according to the criteria proposed by the Subcommittee of Standardization of Lupus Anti-coagulants Phospholipid-dependent Antibodies 149 . Anticardiolipin antibodies must be measured using a standardized ELISA for p2-glycoprotein I-dependent antibodies medium or high titers of IgG and or IgM antibodies are required for a positive result. According to the Sapporo criteria, the diagnosis of definite antiphospholipid syndrome (APS) occurring as a secondary disease in SLE is established when at least one clinical criterion and one laboratory criterion are met. The clinical criteria include thrombotic events and recurrent pregnancy loss 148 . A recent single-center study of 600 SLE patients...

Antinuclear Antibodies

Screening determinations of ANAs are routinely performed by indirect immunofluorescence on cryostat sections of rat liver, kidney, and stomach as well as on HEp2 cell slides. Most commonly, a homogeneous or speckled immunofluorescence pattern is detectable in all three tissues. The most precise definition of an ANA pattern is obtained using HEp2 cells, a cell line derived from laryngeal carcinoma with prominent nuclei. ANAs represent the most common autoanti-bodies in AIH and occur in high titers, usually exceeding 1 160. However, the titer does not correlate with disease course, disease activity, prognosis, progression, requirement of transplantation, or disease reoccurrence after transplantation. Furthermore, ANAs are not specific for autoimmune hepatitis and can also be detected in other autoimmune disorders such as systemic lupus erythemato-sus. In the future, more refined techniques using recombinant nuclear antigens and immunoassay formats may enable the identification of...

C DNA Topoisomerase I 100110 kDa

On calreticulin, Ku70, and Ku80 antigens, 60S ribosomal protein P2, filaggrin, histidyl-tRNA synthetase, and PM Scl 100 antigen. The examples we have selected are (1) proteinase-3, a 29-32-kDa serine proteinase recognized by antibodies from patients with Wegener's granulomatosis (for a review on proteinase-3 epitopes, see 215 ) (2) calreticulin, a 46-kDa calcium-binding protein with multiple regulatory functions that is targeted by autoantibodies in various diseases, including SLE, subacute and neonatal lupus, SS, RA, MCTD, hepatic and celiac disease, and hepatocellular carcinoma, as well as some parasitic diseases and (3) DNA topoisomerase I, a 100-110-kDa nuclear protein that relaxes super-coiled DNA for cellular functions such as replication, recombination, transcription, and DNA repair. Anti-DNA topoisomerase I antibodies are disease-specific diagnostic marker antibodies for SSc. Figure 9.3 presents the results obtained in humans by using synthetic peptides in different test...

Heterogeneity of the Autoimmune Response

Uniform among patients with the same disease but may be heterogeneous with regard to the AAB's isotype, affinity avidity, and epitope specificity as well as with regard to the intra- and intermolecular epitope spreading. Those variations may be in part responsible for differences in the results obtained by different AAB detection assays (see Section 10.2.4) and in variations in AAB profiles, in the pathogenicity of AABs, and in the clinical course of the disease. For example, proteinase 3 (PR3) antibodies of different patients with Wegener's granulomatosis (WG) recognize a limited number of epitopes of overlapping regions on PR3, but with interindividual differences in epitope specificity at the time of diagnosis and with intraindividual changes of epitope specificity during the course of disease 3 . Further investigation is required to determine whether the epitope specificity is responsible for the pathogenicity of PR3 autoantibodies. Anti-dsDNA antibodies in sera of patients with...

Crossreactivity of Autoantibodies with Synthetic Peptides and the Cognate Protein

Numerous studies of autoimmune sera and monoclonal autoantibodies using synthetic peptides to identify epitopes of a protein have failed to locate autoepi-topes in the sequence of the cognate protein. This finding was expected since it is well known that short peptides rarely mimic the conformational epitopes that constitute the large majority of antigenic sites of a protein or a complex. Such results, although always disappointing, are generally well accepted. However, systematic studies of several autoantigens have revealed the presence, in sera from patients or from lupus-prone mice, of antibodies reacting with peptides but not with the whole protein itself. These antibody subsets coexist with other antibody subpopulations reacting with both the peptides and the full-length parent protein or with the whole protein only. The presence of the former antibody population often has been ignored because, in general, investigators first select sera that react with a particular protein,...

Moderate Severe Acute Crohns Colitis

Infliximab and other anti-TNF agents have also been associated with increasing titers of antinuclear and anti-double stranded DNA (dsDNA) antibodies that, rarely, can be associated with a drug-induced lupus syndrome that resolves with discontinuation of anti-TNF therapy. Immunosuppression

Signaling Milieus At The Effector Sites

Treated with prolactin for four weeks, they develop a lupus-like syndrome, with elevated anti-DNA titers, increased numbers of anti-DNA B cells, and an overall shift of B cells from the transitional compartment to the follicular and marginal zone compartments (103). Therefore, it appears that interactions between prolactin and TGF- take different forms to support mucosal immune function in different tissues.

Immediate Twostage Breast Reconstruction

Fibrosis resists effective expansion, limits ultimate projection, and increases the risk of capsule contracture, skin flap necrosis, implant exposure, and infection. Patients with compromised wound healing ability, such as those with scleroderma and lupus, may also benefit from alternative methods.

Comparison of Antigens Conjugates and Cutoff Values

Native antigens may work best for a number of reasons. Some autoantibodies recognize epitopes that are expressed in a macromolecular complex comprised of two or more separate macromolecules. There are diagnostically important antibodies in SLE and drug-induced lupus patients that recognize chromatin but not isolated DNA-free histones or histone-free DNA 55, 56 . Similarly, antibodies recognizing the native RNP particle, but not the individual proteins or RNA moiety, are found in patients with SLE and mixed connective tissue disease 57 . In some cases autoantibodies recognize parts of proteins that are changed by post-translational modifications. The best example of this is the recently discovered autoantibody reactivity in RA patients that recognize only proteins whose arginines have been changed to citrulline 5 . Finally, there are numerous examples of autoantibodies that recognize conformational epitopes that are present on the native form of the protein but not on the denatured...

Fluorodeoxyglucose positron emission tomography

Here we show an example of myocardial deficit of 18F-FDG uptake in a symptomatic patient with systemic lupus erythematosus (SLE) but normal ' 'Thallium scintigraphy (reversed mismatch, Fig. 2)10 The lack of correlation with acute elevation of cardiac enzymes or with ECG changes in SLE patients suggests an underlying chronic process. Such a sensitive technique as 1 8F-FDG-PET may also help to detect myocardial changes in symptomatic BD patients.

Acquired thrombophilia

The antiphospholipid syndrome is the most common cause of acquired thrombo-philia. Identified autoantibodies include lupus anticoagulant and anticardiolipin antibodies. However, there is some evidence that other as yet unidentified auto-antibodies may cause thrombosis and fetal loss in pregnancy. The lupus anticoagulant is so called because it causes a prolongation of the activated partial thromboplastin time even when diluted (because the autoantibody Of women with recurrent miscarriage (three or more), 15 have persistently positive results for phospholipid antibodies. If untreated, 90 will have spontaneous abortions or stillbirths in subsequent pregnancies. It is possible that lupus anticoagulant (30 of cases) and anticardiolipin antibodies (70 of cases) are the same autoantibody identified in different assays. Clinical features of the antiphospholipid syndrome are recurrent fetal loss, thrombosis (arterial and venous), thrombocytopenia, haemolytic anaemia, hypertension, pulmonary...

Measurement of Portal Pressure

Sinusoidal Obstruction Syndrome Sos

Polycythemia rubra vera Paroxysmal nocturnal hemoglobinuria Factor V Leiden Antiphospholipid antibody Lupus anticoagulant Idiopathic thrombocytopenic puprura Nephrotic syndrome Protein losing enteropathy Myeloproliferative disorders Protein C, S or antithrombin deficiency Factor II, VIII, X and XI deficiency Homocysteinuria Hepatitis Trauma Membraneous web (25 ) (usually suprahepatic inferior vena cava)

Acrokeratosis paraneoplastica of Bazex and Dupre

Paraneoplasia Bazex

The two extremes of the disease may coexist. In these cases, the proximal third of the nail is atrophic and the distal two-thirds exhibits hypertrophic changes. The histopathological changes are non-specific, although they do enable the exclusion of a diagnosis of psoriasis, lupus erythematosus or other similar eruptions.

AntiRoSSA and AntiLaSSB

The presence of anti-Ro SSA and anti-La SSB autoantibodies is associated with subacute cutaneous lupus erythematosus 107 , photosensitivity, secondary Sjogren's syndrome, and neonatal lupus 108 . Neonatal lupus provides perhaps the strongest clinical evidence for a pathogenic role of these autoantibodies. This syndrome, related to the presence of anti-Ro SSA and anti-La SSB antibodies in the mother, is characterized by skin rash, cytopenia, cholestasis, and or congenital heart block (CHB) 108 . In recent prospective studies of women with anti-Ro SSA antibodies, the risk of complete CHB was found to be 1-2 109, 110 and of transient cutaneous neonatal lupus about 5 110 . Of note, no ef

Antibodies to Nucleosomes Chromatin

Antibodies to nucleosomes have had a comeback in the last few years. This has to do with both the clinical utility of these antibodies in the diagnosis of SLE and drug-induced lupus (DIL) and new evidence suggesting that nucleosomes may be major candidate autoimmunogens in lupus. Since it is generally accepted that anti-nucleosome antibodies cause the LE cell phenomenon, they were actually among the first autoantibodies discovered. Of note, autoantibodies against individual components of nucleosomes, i.e., DNA or histone, cannot induce LE cell formation. For decades, the LE cell test introduced in 1948 was one of the most common immunological tests performed in clinical laboratories to diagnose SLE. Different names for anti-nucleosome antibodies have caused some confusion. They have been referred to as anti-DNP or anti-sNP antibodies in older publications and as anti-nucleosome, anti-chromatin, and anti-(H2A-H2B)-DNA antibodies in more recent articles 31-33 . The new strategy in lupus...

Anticalpastatin Antibodies

Previously reported and that the prevalence was not significantly different between RA and other rheumatic diseases 43-46 . However, on the other hand, a recent report shows that anti-calpastatin reveals the high prevalence (82 sensitivity) and is exclusively detected (95 specificity) in RA patients 47 . Such discrepancy in the results might reflect the different assay systems, since in the former reports the synthetic C-terminal peptide containing 27 amino acids or recombinant domain I peptide was used for ELISA, whereas human erythrocyte calpastatin was utilized in the latter study. Other reports suggest that anti-calpastatin antibodies are associated with inflammatory-active scleroderma 48 , lupus vasculitis 44 , and deep vein thrombosis 49 . However, the true disease specificity and clinical significance of anti-calpastatin antibodies remain to be determined.

Clinical Box 21 Graft Versus Host Disease

A main reason for the shortage of transplant organs is the fact that the tissues of the donor and the recipient need to match for successful transplantation. Tissues are matched when they have a similar pattern of cell surface proteins. Cell surface proteins are in fact glycoproteins due to the carbohydrates (sugars) attached to their surface. The carbohydrate acts as a flag designating the cell as belonging to the individual. The cellular gly-coprotein pattern may specify an individual within a species or specify a species. If a particular sugar is missing from the surface of a cell, the immune system may recognize this cell as foreign and try to kill it. An attack on self tissue may lead to autoimmune diseases, where the autoimmune reaction can be directed against a specific tissue such as the brain in multiple sclerosis or the digestive tube in Crohn disease. In other cases, the overly active immune system may attack many cells and tissues so that various organs are affected such...

Relationship between Atherosclerosis and Hyperhomocysteinemia

A number of prospective studies have reported the risk estimates of arterial events or vascular and or total mortality conferred by homocysteine in populations without vascular disease at baseline 4-29 . A careful meta-analy-sis of relevant studies by the Homocysteine Studies Collaboration focused on the association between homocysteine concentration and risk of ischemic heart disease and stroke in populations without existing cardiovascular disease, diabetes mellitus, renal disease or systemic lupus erythematosus 51 . The meta-analysis showed that a 25 lower plasma homocysteine (about 3 mol l) was independently associated with an 11 (95 CI 4-17 ) lower risk of ischemic heart disease, and a 19 (95 CI 5-31 ) lower risk of stroke (fig. 1). Studies that were published after this report do not substantially differ from these results 16, 18, 26-29 . Overall, plasma homocysteine, therefore, seems to be a modest, but significant independent predictor of arterial occlusive disease in...

ANCAassociated Vasculitides

ANCA-associated vasculitides, which include Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), are characterized by interactions between anti-neutrophil cytoplasm autoantibodies (ANCAs) and neutrophils initiating endothelial and vascular injury. Focal necrotiz-ing lesions are the common vascular pathology of the ANCA-associated disorders. According to the localization and severity of those lesions, a variety of symptoms and signs can be seen. In contrast to anti-glomerular basement membrane disease, IgA nephropathy, or lupus nephritis, the immunohistology shows little deposition of immune reactants. Myeloperoxidase (MPO) was identified as the target antigen of MPA-associated ANCAs, and proteinase 3 (PR3) as that of WG-associated ANCAs 60, 61 . ANCAs are determined by IIF using ethanol-fixed human neutrophils and by ELISA using MPO or PR3 as target antigen. Most PR3 antibodies produce a granular cytoplasmic (cANCA) pattern, whereas most MPO...

Role of Lselectin in disease

In addition to cell-surface adhesion molecules, the soluble forms of these molecules have been receiving an increasing amount of attention. While soluble adhesion molecules have been used successfully as markers of inflammation or disease activity, their role in physiological processes must also be considered (reviewed in 252 ). Specifically, significantly increased levels of sL-selectin have been reported to be associated with a number of different disease conditions including chronic myeloid and lymphocytic leukemia 253-255 , sepsis 19, 256 , HIV infection 19 , atopic dermatitis 257 , psoriasis 258 , and lupus 259 . As discussed above, since sL-selectin retains functional activity, these increased levels may have important physiological effects on leukocyte migration in these patients. In fact, higher levels of sL-selectin in acute myeloid leukemia patients at the time of diagnosis correlated with decreased probability of achieving complete remission, shorter event-free survival,...

Introduction and Historical Perspective

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease that can involve almost any organ of the human body. The diverse clinical manifestations of SLE are accompanied by a huge number of autoantibodies. The number of antibodies associated with SLE was recently reported to be 116 1 . No other autoimmune disease is similar to SLE with regard to the vast number of autoantibodies linked with it. SLE autoantibodies can react with nuclear, cytoplasmic, and surface cellular antigens as well as with complement components and coagulation system factors.

Peptides Containing Nonnatural Modifications

Peptide analogues containing modified peptide bonds have also been tested with autoimmune sera. Thus, the activity of retro-inverso peptide analogues of the sequences 130-135 ofhistone H3, 304-324 of Ro60 protein, and 277-291 of Ro52 protein has been evaluated with the sera from lupus mice and patients with SLE and SS 159 . In these analogues, also referred to as retro-all-D pep-tides, the amino acid side chains are oriented in the same way as in the original sequence, while the direction of the CO-NH bond in the backbone is reversed 163, 164 . Depending on the sequences, the retro-inverso analogues were recognized by autoantibodies as well or even better than their natural counterpart 159 . Since autoimmune sera generally contain elevated levels of proteases due to peripheral inflammation in autoimmune individuals, such stable analogues might represent valuable probes for immunodiagnostic assays. Their stability in the serum of autoimmune mice or in the presence of protease cocktails...

Autoantibodies in Experimental Models of Autoimmunity

The third type of model does not require any manipulation of the animal at all, as the disease develops spontaneously. The best described of these are the murine strains BXSB, (NZBxNZW) F1, NZM, MRL Fas+ +, and MRL Fasp which develop forms of SLE that serve as excellent models of the autoantibody specificities and pathology of the human disease 63 . Dwight Kono provides an overview of the genetics leading to autoimmunity in these models in Chapter 23. While the variety of autoantibodies developed by these different strains continues to be investigated, the common autoantibody response, like human SLE, is against chromatin and its subcomponents including DNA 38, 64 . In the (NZBxNZW) F1 strain, autoimmune disease and autoantibodies occur earlier and more frequently in female mice, a finding that has been revealed to be associated with the presence of female sex hormones. Because of this and other features, the (NZBxNZW) F1 strain is considered the best animal model of human SLE. As...

The Autoepitope Resides at or in Close Proximity to the Functional Region or Binding Site of the Antigen

Studies were continued comparing the properties of human autoantibodies to antibodies experimentally produced by immunization. Proliferating cell nuclear antigen (PCNA) was first observed in an immunoprecipitation reaction between lupus serum and an antigen in thymus extracts 9 . It was noted that activated lymphocytes undergoing proliferation contained high amounts of the antigen and hence the designation of PCNA given to this antigen. PCNA was shown to

Antiribosomal P Antibodies

This amino acid motif is also present in several microorganisms, which raises the possibility of a molecular mimicry mechanism in the development of anti-P antibody in lupus. Some anti-ribosomal P antibodies cross-react with other autoantigens, particularly the Sm D and Sm B B' spliceosomal subunits 133 , nu-cleosomal molecules, and DNA 134 . As in the case of anti-dsDNA, anti-riboso-mal P antibodies also are capable of penetrating living cells and of profoundly suppressing protein synthesis 135 . The reported prevalence of anti-ribosomal P antibodies in SLE ranges from 10-40 prevalence is higher in Asian patients than in black and Caucasian patients 136 . A correlation between anti-ribosomal P and lupus psychosis was reported soon after the discovery of this antibody 127 . Several subsequent studies confirmed this association and also reported an association with depression 137, 138 , although other researchers disagree 139 . Anti-ribosomal P antibody correlates with the activity of...


In only a few diseases have autoantibodies been shown to be the causative agents of pathogenesis (e.g., anti-acetylcholine receptor autoantibodies in myasthenia gravis, anti-thyroid-stimulating hormone receptor autoantibodies in Graves' disease) 30, 31 . It is noteworthy not only that these diseases are organ specific but also that their autoantigens are extracellular or on the surface of cell membranes and therefore easily targeted by the immune system. In some individuals the largest organ, the skin, can suffer insult from several blistering conditions now known to be autoimmune diseases characterized by autoantibodies against products of keratinocytes 32 . The autoantigens involved are cell adhesion molecules that are important in maintaining the integrity of the skin by cell-cell contact between the various cell layers in the epidermis and at the dermal-epidermal junction. In the non-organ-specific autoimmune disease systemic lupus erythematosus (SLE), anti-double-stranded DNA...


Cyclosporine has been used again extensively during pregnancy in renal transplant patients and patients with systemic lupus erythematosus (SLE) (Bermas and Hill, 1995). The medical literature reports cyclosporine use to avoid colectomy in a few pregnant patients without fetal loss. However, nephrotoxicity, hypertension, and hepatoxicity are commonly reported in the pregnant patient and these are potential side effects of cyclosporine. One must therefore weigh the risk of medication toxicity versus urgent colectomy in the pregnant patient with severe colitis.

Figure 1127

Survival of patients with systemic lupus erythematosus (SLE) on dialysis. Although initially dialysis treatment was not offered to patients with SLE because of the systemic nature of their illness, it later became clear that patients with SLE tolerate dialysis treatment as well as do patients with non-SLE renal diseases. The overall patient survival is good (90 at 5 years), and no differences exist in patient survival between those treated with continuous ambulatory peritoneal dialysis (CAPD) as compared with hemodialysis. (Data from Nossent et al. 65 .)

Figure 1130

Lupus disease activity after renal transplantation. Disease activity was assessed in 28 patients with systemic lupus erythematosus (SLE) by calculating the maximal nonrenal SLE Disease Activity Index (SLEDAI) in the time periods before dialysis, during dialysis, and after renal transplantation. The maximal nonrenal SLEDAI scores were divided in three groups 0, no extrarenal disease activity 1 to 10, moderate extrarenal disease activity over 10, high extrarenal disease activity. Note that before dialysis all patients had extrarenal lupus disease activity but that after renal transplantation no patient had high disease activity. These data illustrate that the decrease in disease activity that begins during dialysis treatment continues after renal transplantation. In addition, recurrence of lupus nephritis after renal transplantation is rare 67 . (From Berden 14 with permission. Data from Nossent et al. 68 .)

Figure 1128

Severity of systemic lupus erythematosus (SLE) disease activity during hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Lupus disease activity generally decreases during dialysis treatment. As assessed by the SLE Disease Activity Index (SLEDAI) 66 , the maximal nonrenal SLEDAI decreased during dialysis in 49 of patients, remained stable in 42 , and showed progression in 9 . Despite the fact that immunosuppression was minimized, in 90 of patients cytotoxic drug therapy was discontinued and in 55 the dose of steroids was considerably reduced 65 . In addition, in this analysis no differences were found in disease activity in patients treated with either hemodialysis or CAPD. The maximal nonrenal SLEDAI scores were divided in three groups 0, no extrarenal disease activity 1 to 10, moderate extrarenal disease activity over 10, high extrarenal disease activity.

Figure 1129

Graft and patient survival after renal transplantation in patients with systemic lupus erythematosus (SLE). For this analysis only patients with first transplantations using a cadaveric donor kidney were included. Both graft and patient survival were calculated for 165 patients with SLE who received transplantation between 1984 and 1992. These data are compared with the results in 21,726 patients with non-SLE glomerular diseases who received transplantation in the same time period. Both graft and patient survival were not significantly different between the two groups. (From Berden 14 with permission. Data from G. Persijn, Eurotransplant, Leiden, the Netherlands.)

Figure 740

Proliferative glomerulonephritides represent instances of postinfectious glomerulonephritis or manifestations of hepatitis C co-infection 196-199 . Alternatively, proliferative glomerulonephritides may result from renal depository of preformed circulating immune complexes with specificity for HIV proteins and are HIV-associated 199 . In patients infected with HIV, membranous glomerulonephritis has been associated with hepatitis B, hepatitis C, syphilis, and systemic lupus erythematosus 198,200-203 . Lupus-like nephritis has been reported in children and adults with HIV infection in association with membranous, mesangial, and intracapillary proliferative glomerular lesions 204 . IgA nephropathy has been reported in association with HIV infection. The occurrence of IgA nephropathy may not be coincidental and is HIV-associated. Indeed, circulating immune complexes composed of idiotypic IgA antibody reactive with anti-HIV IgG or IgM were identified in two patients, and the identical...

Figure 611

Immunohistologic examination utilizing monoclonal antibodies, coupled with conventional and electron microscopy, indicates that most of the mononuclear inflammatory cells comprising renal interstitial infiltrates are T cells. These T cells are immunologically activated in the absence of any evidence of tubulointerstitial immune deposits, even in classic examples of immune complex-mediated diseases such as systemic lupus erythematosus. The profile of immunocompetent cells suggests a major role for cell-mediated immunity in the tubulointerstitial lesions. The infiltrating cells may be of the helper-inducer subset or the cyotoxic-suppressor subset, although generally there seems to be a selective prevalence for the former variety. Lymphocytes that are peritubular and are seen invading the tubular epithelial cells, so-called tubulitis, are generally of the cytotoxic (CD8+) variety.

Breaking Tolerance

Even in autoimmune mouse strains where B-cell defects have been described, T cells are necessary for full expression of autoimmune disease (reviewed in 100 ). Of all the B-cell tolerance mechanisms, only deletion, the ultimate form of tolerance, can resist strong T-cell drive. However, there is no shortage of newly emerging autoreactive B cells that escape negative selection and receptor editing in a recent study 4 of the normal, mature B-cell repertoire had autoreactivity to native DNA 82 , the prototypic target of autoantibodies in systemic lupus erythematosus (see Chapter 11). Furthermore, somatic mutation driven by Th and self-antigen could readily convert weakly autoreactive B cells to produce high-affinity autoantibodies 101 . Taken together, it is difficult to escape the conclusion that the onus for control of immune tolerance is the predominate purview of the T-cell repertoire.


Become apparent when a renal biopsy is performed. Recently, immunoglobulin A (IgA) nephropathy has been reported as an increasingly frequent cause of malignant hypertension. In one series of 66 patients with IgA nephropathy, 10 developed malignant hypertension 3 . Chronic atrophic pyelonephritis in children, often a result of underlying vesicoureteral reflux, is the most common cause of malignant hypertension 4 . In Australia, malignant hypertension complicates up to 7 of cases of analgesic nephropathy 5 . Transient malignant hypertension responsive to volume expansion has been reported in analgesic nephropathy. It has been suggested that interstitial disease with salt-wasting is important in the patho-genesis by causing profound volume depletion with activation of the renin-angiotensin axis. Malignant hypertension is both an early and late complication of radiation nephritis that can occur up to 11 years after radiotherapy. Renovascular hypertension from either fibromuscular...

Figure 810

Differential diagnosis of granulomatous lesions in renal sarcoidosis. Once considered rare, granulomatous interstitial nephritis is now observed in 10 of kidney biopsy results. Most of these are seen in cases of drug hypersensitivity. The commonly implicated drugs are antibiotics and nonsteroidal anti-inflammatory drugs. Sarcoidosis and Wegener's granulomatosis each account for 5 to 10 of cases observed on kidney biopsy. Other less common and rather rare causes include tuberculosis, angiitis, and lupus erythematosus. In some 15 to 20 of cases, the cause of the granulomatous lesions is never established.

Figure 175

The prevalence and incidence of recurrent disease after transplantation is difficult to ascertain. Certainly, system lupus erythematosus and idiopathic rapidly progressive glomerulonephritis rarely recur in grafts, whereas in some groups of patients recurrence of focal segmental glomerulosclerosis is universal 4 . There is much debate as to the frequency of recurrence of immunoglobulin A disease and whether there is any association of recurrence with graft dysfunction

Figure 109

In the second or third trimester of pregnancy a clinical flare-up of lupus may be difficult to distinguish from preeclampsia. Treatment of a lupus flare-up might involve increased immunosuppression, whereas the appropriate treatment of preeclampsia is delivery. Thus, it is important to accurately distinguish these entities. Preeclampsia is rare before 24 weeks' gestation. Erythrocyte casts and hypocom-plementemia are more likely to be a manifestation of lupus, whereas abnormal liver function test results are seen in preeclampsia and not usually in lupus. C complement minus sign absent plus sign present PE preeclampsia SLE systemic lupus erythematosus.

Figure 1121

Incidence of the different forms of lupus nephritis classified according to the World Health Organization (WHO) classification. The incidence of the different forms categorized according to the WHO classification depends on patient selection and ethnic background. The percentages represent an average of the data reported in the literature. Most patients have a diffuse proliferative form of lupus nephritis (WHO class IV).

Figure 1122

Incidence of renal manifestations and serologic abnormalities in the different forms of lupus nephritis. The clinical manifestations of lupus nephritis are not different from other forms of glomerulonephritis and include a nephritic sediment (dysmorphic erythrocytes and erythrocyte casts), proteinuria or nephrotic syndrome, impaired renal function, and hypertension. Although certain clinical manifestations are more prevalent in certain forms (nephrotic syndrome for World Health Organization (WHO) class V, nephritic sediment for WHO class IV), it is clear that on the basis of clinical symptoms it is not possible to classify the form of nephritis correctly. This inability underlines the necessity for obtaining a renal biopsy specimen. In addition, listed are the occurrence of both a positive result on performing a Farr assay and a low complement 3 level for the different forms of lupus nephritis. Anti-dsDNA anti-double-stranded DNA. (Adapted from Appel et al. 50 ).

Figure 1115

A, Segmental necrotizing lesion surrounded by an increased number of epithelial cells. B, Immunofluorescence. Next to mesangial deposits of immuno-globulin G there also are deposits in the periphery of some loops (arrows). C, Immunofluorescence. Fibrin deposits in a necrotizing lesion. According to the 1995 modified World Health Organization classification, this is a characteristic immuno-pathologic lesion of class III lupus nephritis. (Panel A, methenamine silver. Original magnification X400, X400, X520, respectively.)

Figure 1116

Lupus nephritis class IV on light microscopy and immunofluorescence. A and B, Diffuse endocapillary proliferative pattern of injury with an increase of mesangial cells and an influx of mononuclear cells and some granulocytes. Panel B shows a necrotizing lesion (arrow). C, A mesangio-capillary pattern of injury with duplication of the glomerular basement membrane (GBM), an increase of mesangial cells and matrix, and massive subendothelial deposits (wire loops). In addition, spikes (membranous component) can be found on the epithelial side of the GBM (arrow). D, Immunofluorescence. The characteristic pattern of the immune deposits (immunoglobulin G) of class IV lupus nephritis, predominantly localized along the capillary wall. (Panels A, B, C, methenamine silver. Original magnification X360, X360, X740, X300, respectively.)

Figure 1123

Treatment options for the different forms of lupus nephritis are summarized. Only for World Health Organization (WHO) classes III, IV, and V are a limited number of prospective studies available. For the other forms, a balanced compilation is made from the literature and personal experience. Reference 14 supplies a more detailed analysis of the therapeutic options. For class I lupus nephritis, no specific renal therapy is necessary treatment is dictated by the presence of extrarenal symptoms. In general, patients with class II lupus nephritis respond satisfactorily to monotherapy with oral corticosteroids. The patient, however, For patients with classes III and IV lupus nephritis, corticosteroid monotherapy is not sufficient (Fig. 11-24). Cytotoxic immunosuppressive therapy, either cyclophosphamide or azathioprine, should be added to the treatment. The choice of one of these drugs over the other is discussed in Figures 11-24, 11-25, and 11-26. According to a recent analysis 51 ,...

Figure 225

Chest radiograph of alveolar hemorrhage. This patient has antiglomerular basement membrane-mediated glomerulonephritis complicated by pulmonary hemorrhage (Goodpasture's disease). Note the butterfly appearance of the alveolar infiltrates characteristic of intrapul-monary (alveolar) hemorrhage. Such lesions can also occur in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis and glomerulonephritis, lupus nephritis (SLE), cryoglobulinemia, and rarely in Henoch-Schonlein purpura (HSP).

Figure 1118

A, Discrete spikes on the epithelial side of the glomerular basement membrane (GBM) (arrows), and a moderate increase of mesangial cells. B, Immunofluorescence. Fine granular deposits of immunoglobulin G along the capillary wall in a characteristic membranous pattern. C, Electron micrograph reveals electron-dense deposits on the epithelial side of the GBM between spikes. Between an increased number of mesangial cells small deposits also are present (arrows). L capillary lumen S spikes U urinary space. (Panel A, methenamine silver, original magnification X700, X400, X3100, respectively.)

Other Cytokines

Several other T cell- or B cell-derived cytokines may also participate in the pathogenesis of humoral autoimmune diseases. For example, IL-5, produced by T cells, has been demonstrated to exacerbate autoantibodies in a murine model of AIHA 161 as well as in the (NZB x NZW) Fj murine lupus model 81 . Prior studies have implicated IL-12 which is primarily produced by macrophages but is also produced by B cells 171 - in the pathogenesis of EAT 172 , EAMG 106, 173 , (NZBxNZW) Fj, and MRL lpr lupus 111, 174 , as well as in collagen-induced arthritis 175 . But other studies have suggested that it may be protective, at least in mercury-induced autoimmunity 176 and GVHD 177, 178 . However, given the recent discovery of multiple members of the IL-12 family that share common active subunits, such as IL-23 and IL-27, these findings are likely confounded and thus require revisitation 179 . Finally, soluble forms of surface receptors, such as soluble CD154 180, 181 , have been described in these...

Figure 1113

The value of the analysis of lupus glomerulonephritis according to the World Health Organization (WHO) classification for prognosis and treatment can be enhanced by including indices of activity and chronicity. These indices were proposed in the National Institutes of Health (NIH) index 49 . The extent of the active and chronic lesions is assessed according to the scoring system here. A chronici-ty index of 3 or higher and an activity index of 12 or higher are associated with a significantly greater risk for the development of end-stage renal disease 14 .

Figure 99

Immunohistochemical staining with anti-monocyte-macrophage antibody (CD68). This reaction confirms that the intracapillary hypercellularity is due mainly to accumulation of these mononuclear leukocytes. Their average number in acute stages of cryoglob-ulinemic glomerulonephritis is four times greater than in severe proliferative lupus nephritis 15 . (Immunoperoxidase X 250.)


Table 5.1 Costimulatory interventions in systemic lupus erythematosus3'. Table 5.1 Costimulatory interventions in systemic lupus erythematosus3'. a) Effect of blocking antibodies or genetic deficiencies on the autoimmune syndromes of humans and mice with lupus. Significant versus mild reductions in the indicated disease parameters are indicated by jj and j, respectively significant versus mild exacerbations in the indicated disease parameters are indicated by and respectively no significant difference in a disease parameter is indicated by a) Effect of blocking antibodies or genetic deficiencies on the autoimmune syndromes of humans and mice with lupus. Significant versus mild reductions in the indicated disease parameters are indicated by jj and j, respectively significant versus mild exacerbations in the indicated disease parameters are indicated by and respectively no significant difference in a disease parameter is indicated by Nonetheless, the dominant importance of CD40-CD154 in...

AZA and Metabolites

Experience with immunomodulators in pregnant patients with renal transplants and systemic lupus erythematosis yields no teratogenecity or other adverse events. Physicians and patients should discuss the use of AZA and 6-MP for maintenance of remission during pregnancy especially if the disease activity was severe prior to beginning the medication. Controversy exists in the literature regarding the safety of AZA and 6-MP for childbearing female and male patients. In a recent publication, Francella, Present and colleagues reviewed the records of 155 IBD patients who had conceived at least one pregnancy after developing IBD. There were 325 pregnancies and 18 elective abortions. Seventy-nine of the patients were female and they had 171 pregnancies (median 2). There were 154 pregnancies from the 76 male patients. One involved 65 pregnancies with parents who had not been on 6-MP. There was no statistical difference in spontaneous abortions, abortions sec-

Figure 1150

The mainstay of treatment for patients with scleroderma renal crisis, because it will significantly reduce progression to renal failure, increase the chance of recovery if renal failure has already developed, and improve the 1-year patient survival rate. Renal replacement therapy (hemodialysis or continuous ambulatory peritoneal dialysis) should be offered to patients whose renal function does not recover. The patient survival rate, however, is lower than in patients with other collagen-vascular diseases such as lupus nephritis. Limited experience with renal transplantation indicates that successful transplantation is possible, especially in patients with quiescent disease. Recurrence in the transplanted kidney has been reported 84 . References 96 to 98 provide more extensive reviews on the subject.


Optical biosensors have been used for a large range of immunological applications. They can be used for quick measurements of biomolecular interactions in real time without requiring label reactants. Many review articles have analyzed the scope and limitations of optical biosensors 100, 101 . In the domain of autoepitope mapping with peptides, however, very few reports have been published. They concern, for example, the characterization of major epitopes recognized by cANCA in the proteinase-3 using the surface plasmon resonance BIA-core biosensor 102 and the test of monoclonal autoantibodies generated from lupus mice using nucleosomes, dsDNA, and peptide 83-100 of histone H3 103 . Screening for epitope-specific autoantibodies using biotinylated peptides immobilized on streptavidin chips in the BIAcore system has also been used to detect autoantibodies against the 51-adrenergic receptor in sera of patients with idiopathic dilated cardiomyopathy 104 and the angiotensin II receptor 1 in...

Other Compounds

Experimental models of lupus and diabetes than methimazole 98 . The phenyl analog inhibited TNF-a-induced VCAM-1 mRNA and protein expression in human airway epithelial cells (HAECs), reduced TNF-a-induced monocytic (U937) cell adhesion to HAECs under in vitro flow conditions, inhibited TNF-a-induced interferon regulatory factor-1 (IRF-1) binding to VCAM-1 promoter, and reduced TNF-a-induced IRF-1 expression in HAECs 95 .

AntiDNA Antibodies

There is a high potency of anti-DNA antibodies to cross-react with non-DNA antigens such as laminin, heparan sulfate, type IV collagen, and a-actinin, which are located in the kidney. The cross-reactivity with renal antigens may contribute to the pathogenesis of lupus nephritis in which anti-DNA antibodies clearly play a central role 24, 25 . Recently, it was demonstrated that the penta-peptide Asp Glu-Trp-Asp Glu-Tyr-Ser Gly is a molecular mimic of dsDNA. The sequence that is also present in the extracellular ligand-binding domain of mur-ine and human N-methyl-D-aspartate (NMDA) receptor subunits NR2a and NR2b is recognized by a subset of both murine and human anti-DNA antibodies. These antibodies can signal neuronal death and can be detected in the cerebrospinal fluid of SLE patients 26 . Very recently, an association between neuropsychiatric disturbances in SLE and antibodies against a decapeptide containing this sequence motif present in the extracellular NMDA receptor was shown...

Figure 433

Scleroderma associated with Raynaud's phenomenon, disseminated lupus erythematosus, and causalgia of the median nerve. The condition may be idiopathic, congenital, and familial or acquired. A congenital, aberrant, painful hyponychium has been described associated with oblique, deep fractures of the nails. In one case an unusual acquired association of pterygium inversum unguis and lenticular atrophy of the palmar creases was recorded.

Figure 1125

A, The probability of end-stage renal disease in patients with proliferative lupus nephritis treated with different drug regimens. This update of the prospective trial by the National Institutes of Health (NIH) on the treatment of these patients clearly demonstrates that prednisone monotherapy, in a significantly greater proportion of patients, leads to the development of end-stage renal disease compared with patients on regimens containing cytotoxic drugs. The results between azathio-prine and drug regimens containing cyclophosphamide are not significantly different. Note that in up to 7 years the results do not differ between the different treatment groups. From these studies it is clear that although the therapeutic efficacy is equal for the three treatment regimens containing cyclophosphamide, less side effects occurred in patients treated with intravenous pulses of cyclophosphamide. B, Renal survival in patients with World Health Organization (WHO) class IV lupus nephritis...

Anti Clq Antibodies

Fied postmortem in the glomeruli of four of five patients with proliferative glomerulonephritis. The concentrations of these autoantibodies in the glomerular tissue was at least 50 times higher than the serum concentration this is the first evidence suggesting that anti-C1q autoantibodies collect and concentrate in the renal glomeruli of patients with SLE. Therefore, anti-C1q autoantibodies may contribute to the pathogenesis of lupus glomerulonephritis 170, 171 . Conversely, lupus nephritis does not develop in the absence of anti-C1q autoantibodies, 172, 173 . Anti-C1q autoantibodies also occur in murine models of SLE 174, 175 . A recent study showed that anti-C1q antibodies cause renal pathologies in combination with glomerular C1q-containing immune complexes 176 .

Figure Itit

Nephritis caused by systemic lupus erythematosus (SLE) rarely recurs in transplantations. SLE accounts for approximately 1 of all patients receiving allografts, and less than 1 of these will develop recurrent renal disease. Time to recurrence has been reported as 1.5 to 9 years after transplantation 24,25 . Cyclosporine therapy does not prevent recurrence. It is reasonable to ensure that serologic test results for SLE are minimally abnormal before transplantation and certainly that patients have no evidence of active extrarenal disease. Patients with lupus anticoagulant and anticardiolipin antibodies are at risk of thromboembolic events, including renal graft vein or artery thrombosis. These patients may require anticoagulation therapy, or platelet inhibition with aspirin.


The same strategy was used to identify DNA mimotopes recognized by antibodies from lupus patients (reviewed in 185 ). A series of DNA mimotopes was identified using monoclonal or polyclonal antibodies from lupus individuals and mice, corresponding, for example, to the sequences D EWD EEYS G 186189 , RLTSSLRYNP 190 , or XXXDCTXNT CQL Y DXE (where is an aromatic residue F, Y, or W and X is any residue) 191 . A 44-amino-acid fragment recognized by pathogenic anti-DNA antibody 3E10 has also been identified 192 . Contrary to the findings of other studies, this monomeric peptide was found to correspond to a sequence of HP8, a protein of the osteonectin SPARC family of extracellular matrix proteins. Several experiments including mutagen-esis have demonstrated that binding of both dsDNA and HP8 protein occurs through overlapping portions of the antibody-binding site.


Observations made in human autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, polymyositis, and related autoimmune rheumatic diseases. These studies have shown that the autoantibody response to a self-antigen may be unlike an immune response to a foreign antigen or to a laboratory-purified autologous antigen. One of the special features of the humoral autoimmune response is that the autoantigens are highly conserved molecules, but, in the fine details, the conserved antigenic determinant is a complex epitope that consists of conformation-dependent discontinuous regions of the self-molecule. This autoepitope appears to be the functional site or the interactive binding region of the molecule. These findings are in striking contrast to the immune response to a foreign antigen. An important issue that needs to be resolved in the puzzle of autoimmunity is the elucidation of the mechanisms whereby the host regulates in such a specific manner its own immune...

Jeremy B Levy

Overall, three groups of diseases recur in patients with transplantations metabolic disorders, especially primary hyperoxaluria and diabetes systemic diseases, including systemic lupus erythematosus, sickle cell disease, systemic sclerosis, hepatitis C virus-associated nephropathies and systemic vasculitis and a variety of glomerulonephritides. For immunemediated systemic diseases the standard transplantation immunosuppressive regimens often prevent recurrence of primary

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