Two ro (ss‐a) autoantibody responses in systemic lupus erythematosus

Abstract

Sdnuclear RNP were quantitated by enzyme-linked immunosorbent assay in 106 white patients with systemic lupus erythematosus. Two Ro autoantibody subgroups were identified that differed quantitatively, genetically, and clinically. The subgroup having anti-Ro only demonstrated significantly lower mean anti-Ro levels than did the subgroup with concomitant anti-La and showed a strong association with the linked HLA alleles DR2 and DQwl. The anti-Ro with anti-La sub- group was associated with the linked HLA alleles B8, DR3, DRw52, and DQw2 (DR3 was primary), and this subgroup consisted of patients with older ages at disease onset, sicca complex, and less renal involvement. Overall, the relative risk (RR) for having anti-Ro was highest in HLA-DR21DR3 heterozygotes compared with non-DR2/DR3 heterozygotes (RR 15) and all other DR combinations (RR 7), suggesting a compound effect of 2 immune responses. Heterozygotes for HLA-DQwl/ DQw2 demonstrated significantly higher mean levels of anti-Ro, which may be indicative of trans gene interaction at HLA-DQ. These data suggest the hypothesis that HLA genes exert their major effects on Ro/La autoantibody subsets of systemic lupus erythematosus.Genetic predisposition to systemic lupus erythematosus (SLE) has been associated with several alleles of the major histocompatibility complex (MHC). Those most consistently reported include HLA-B8, DR2, DR3, and DQwl, as well as null alleles of the HLA-linked second and fourth components of complement (1-8). When autoantibody subsets of SLE are considered, certain HLA antigen correlations become stronger. Most notably, in patients with SLE and in patients with other autoimmune diseases expressing anti-Ro and anti-La, HLA-DR3 andlor DR2 are found in the majority (4,5,9-13). Thus, MHC control of these immune responses, either qualitatively or quantitatively, has been suggested. Recently, enzyme-linked immunosorbent assays (ELISA) have been developed to measure anti-Ro, anti-La, and the anti-Sdnuclear RNP (anti-SmhRNP) complex (14)(15)(16)(17)(18)(19)(20). By virtue of being more sensitive and quantitative, these assays may provide greater insight into the role

HLA Class II Influences the Immune Response and Antibody Diversification to Ro60/Sjögren’s Syndrome-A: Heightened Antibody Responses and Epitope Spreading in Mice Expressing HLA-DR molecules

“…Previous studies have demonstrated that the presence of the HLA-DR3-DQ2 haplotype is highly associated with a more diversified La/Ro RNP response, whereas the haplotype HLA-DR2-DQ1 is associated with a less diversified La/Ro RNP response (5,(45)(46). Our previous data (47) also confirmed the association of HLA-DR2 or HLA-DR3 with more diversification of hRo60-induced autoantibodies to involve other RNPs including mRo52, mla, and mouse Sm as detected by immunoblotting.…”

Clinical and Pathological Roles of Ro/SSA Autoantibody System

“…HLA class II phenotype might support epitope spreading. The presence of anti-Ro and/or anti-La antibodies is more strikingly associated with HLA-DR3 and/or HLA-DR2 [103, 104]. HLA-DR3 is associated with both anti-Ro and anti-La antibody production while HLA-DR2 favors anti-SSA antibody synthesis [105].…”

Reactivation of Epstein-Barr virus in Sjögren's syndrome

“…Initial studies s u g g e s t e d that S S -A (also k n o w n as " R o " ) antigen was a single 6 0 -k D a p r o t e i n ; s u b s e q u e n t reports d e m o n s t r a t e d p r o t e i n s r e a c t i v e w i t h a n t i -S S -A antibody including a 5 2 -k D a p r o t e i n in all n u c l e a t e d cells [3] and a 5 4 -k D a p r o t e i n in non-nucleated red blood cells [21,22,31]. Anti-SS-A antibody also is found in low titers in normal adults [ 18] and ina subset of patients with multiple myeloma [361.…”