Autoantibodies to the ribosomal phosphoproteins first described in 1985 are a serological feature of patients with SLE [127, 128]. Rib-P autoantigens consist of three protein components of the 60S ribosomal subunit designated P0 (38 kDa), P1 (19 kDa), and P2 (17 kDa). A pentameric complex composed of one copy of
P0 and two copies each of P1 and P2 interacts with the 28S rRNA molecule to form a GTPase domain, which is active during the elongation step of protein translation. The major immunoreactive epitope of these ribosomal antigens has been localized to the carboxy-terminal domain, which is highly conserved in all three proteins; moreover, it contains two phosphorylated serine residues (e.g., Ser102 and Ser10 of human P2) [129-131]. Several studies have shown that both the acidic and hydrophobic clusters are critical for autoantibody binding and that P protein phosphorylation is not [130, 132]. Furthermore, epitope mapping studies have shown that the major epitope domain is located within the last six C-terminal amino acids (GFGLFD) .
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 , nu-cleosomal molecules, and DNA . 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 .
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 . A correlation between anti-ribosomal P and lupus psychosis was reported soon after the discovery of this antibody . Several subsequent studies confirmed this association and also reported an association with depression [137, 138], although other researchers disagree . Anti-ribosomal P antibody correlates with the activity of lupus , particularly lupus nephritis [141, 142]. Furthermore, the coexistence of anti-dsDNA and anti-ribosomal P antibodies is more closely associated with lupus nephritis than is the presence of either of them alone . Anti-ribosomal P antibody is also associated with lupus hepatitis . Indeed, the association between anti-ribosomal P and lupus hepatitis does not apply to patients with autoimmune hepatitis except when lupus is present; this again emphasizes the high specificity of anti-ribosomal P with lupus .
Although anti-ribosomal P protein autoantibodies were discovered approximately 20 years ago, they have not achieved the same attention and clinical impact as anti-Sm or anti-dsDNA antibodies. This may be due to the limited reliability of ANA screening by indirect immunofluorescence for the detection of anti-ribosomal P antibodies or to the absence of an international reference serum. It is noteworthy that a reference standard human Rib-P antibody has recently become available (Centers for Disease Control, Atlanta, GA: Catalogue #2706). This should be an important step in standardizing assays from different sources.
Because of the high specificity of anti-ribosomal P for SLE, some researchers have put forward the proposal that, like anti-Sm and anti-dsDNA antibodies, Rib-P antibodies should be considered for inclusion as a criterion for the classification of SLE .
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