core--patient accrual and hla serological analysis
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Publication
Journal: Arthritis and rheumatism
January/21/1990
Abstract
In sera from patients with systemic lupus erythematosus or Sjögren's syndrome, we determined the fraction of antibody that remained reactive with human Ro (SS-A) after absorption with bovine spleen extract, and the reactivity with the 60-kd and 54-kd red blood cell Ro (SS-A) bands by Western blot. Of the 3 groups of sera studied, those containing anti-Ro (SS-A) alone had the highest degree of reactivity with human Ro (SS-A) after absorption with bovine spleen extract, followed, in descending order, by sera containing anti-Ro (SS-A) and anti-La (SS-B), and sera containing anti-Ro (SS-A) and anti-nuclear RNP. The groups of sera could be distinguished on this basis. Sera with anti-Ro (SS-A) and anti-nuclear RNP could also be distinguished from the other 2 types of sera by their uniform and preferential reactivity with the 60-kd red blood cell Ro (SS-A), by Western blot analysis. These findings indicate that there are both qualitative and quantitative differences, associated with the presence of other autoantibodies, in the fine specificity of anti-Ro (SS-A) sera.
Publication
Journal: Arthritis and rheumatism
December/12/1993
Abstract
OBJECTIVE
Lupus nephritis has often been associated with anti-DNA, but, based on the findings in eluate studies, it appears that other antigen-antibody reactions, such as those involving anti-Ro/SS-A, anti-nuclear RNP (anti-nRNP), and/or anti-Sm, may also contribute to the pathogenesis of nephritis. In the present investigation, we identified and further studied a distinctive precipitin profile present in black women with nephritis.
METHODS
Longitudinal clinical and serologic studies of a cohort of university-based systemic lupus erythematosus (SLE) patients (n = 120) were carried out over an 8-year period.
RESULTS
A subset of 20 black female patients was identified, of whom 8 had lupus nephritis (group I) and 12 did not (group II). Group I was characterized by a distinct precipitin profile consisting of anti-Ro/SS-A, anti-SM, and anti-nRNP, but no anti-La/SS-B. SLE disease duration at presentation was significantly shorter in group I than in group II (mean 1.94 years versus 5.21 years; P = 0.02). The distinctive precipitin profile of anti-Ro/SS-A, anti-Sm, and anti-nRNP occurred exclusively in group I patients (6 of 8, versus 0 of 12 in group II; P < 0.001). In white lupus nephritis patients, this precipitin profile was not seen.
CONCLUSIONS
While the mechanism responsible for the relationship of this distinctive serologic profile to the development of nephritis in black female lupus patients remains to be determined, its presence may be used as a marker for severe and progressive renal disease.
Publication
Journal: Clinical and Experimental Rheumatology
November/12/1995
Abstract
OBJECTIVE
This study determines the antigenic regions of the nRNP C lupus autoantigen.
METHODS
Twenty-one anti-nRNP C sera, six patients with other autoimmune serology, and five normal control sera were assessed for binding with the overlapping octapeptides of the nRNP C protein. Column absorptions were conducted to assess the percentage of the anti-nRNP response which was directed against one major epitode of nRNP C:
RESULTS
Eleven regions of nRNP C are bound in different combinations by anti-nRNP C patient sera. Neither normal controls nor patients without anti-nRNP C antibodies significantly bind any regions of nRNP C: The antigenic region spanning amino acids 117-126, PAPGMRPP, is recognized by all twelve Sm, nRNP precipitin positive patients tested. Indeed, from 14 to 32% of the anti-nRNP reactivity in Sm, nRNP precipitin positive patient sera is directed against PAPGMRPP: All of these patients also bind a very similar sequence which is repeated three times in the Sm B/B' protein. Patients sera with only anti-nRNP antibodies, however, do not recognize this proline rich sequence as antigenic.
CONCLUSIONS
This elucidation of the specific areas of nRNP C which are important in the autoantigenicity of nRNP C will hopefully lead to a better understanding of the involvement of these autoantibodies in the etiology and pathogenesis of SLE.
Publication
Journal: American Journal of Medicine
January/24/1989
Abstract
Antibodies to the small RNA protein particles Ro/Sjögren's syndrome A (Ro/SSA), La Sjögren's syndrome B (La/SSB), Sm, and U1-ribonucleoprotein (U1RNP) occur characteristically in patients with systemic lupus erythematosus. Although not mutually exclusive, those antibodies tend to occur in pairs; anti-Ro/SSA and anti-La/SSB in one group, anti-U1RNP and anti-Sm in another group. The emerging data suggest that these pairs of immune responses differ in fundamental ways, signifying different mechanisms for their initiation and control. Antibodies to Ro/SSA and La/SSB are strongly associated with the class II antigens DR2 and DR3 and the response is directed to epitopes on the particles that change in evolution. These responses are found frequently in normal persons in low titer but not in animal models of systemic lupus erythematosus. Contrariwise, the immune response to Sm and U1RNP is only weakly associated with class II antigens and the response is to epitopes conserved in evolution. These responses are not found in normal persons but are frequently found in animal models. The implications of these differences are explored.