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.

In 1948, Malcom Hargraves, Helen Richmond, and Robert Morton from the hematology laboratory of the Mayo Clinic in Rochester noted the presence of previously unknown cells in the bone marrow of a patient with acute SLE. These cells, which they called LE cells, were described as mature neutrophilic polymorphonuc-lear leukocytes that phagocytose Feulgen-stained nuclear material [2]. This historic finding ultimately led to the discovery of a broad variety of autoantibodies directed against nuclear antigens, which are now known as antinuclear antibodies (ANAs). In 1949, Haserick and Bortz made the important observation that, when incubated with normal bone marrow, serum from SLE patients was able to induce the formation of LE cells [3]. The inducing factor, called LE factor, was found to be associated with the gamma-globulin fraction of SLE serum [4], which was suspected to be an antibody. For the next 10 years, the detection of LE cells in the peripheral blood remained the most popular laboratory test for the diagnosis of SLE. In 1953, Peter Miescher observed that the sera from rabbits immunized with cell nuclei were able to induce LE cell formation using normal human leukocytes. One year later, Miescher demonstrated that absorption of SLE serum by cell nuclei isolated from calf thymus cells made the serum incapable of inducing LE cell formation. Based on these experiments, the LE factor was confirmed to be an ANA [5]. These pivotal findings resulted in the simultaneous reporting of antibodies to DNA in the sera of SLE patients by at least four different groups in 1957 [5-9].

Because the spectrum of autoantibodies associated with SLE is so broad, this article will focus on autoantibodies of high diagnostic relevance. Table 11.1 summarizes the characteristics of important autoantigen-autoantibody systems in SLE.

A recent publication has shown that autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibod-ies tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic [10].

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