HLA-DQ gene complementation and other histocompatibility relationships in man with the anti-Ro/SSA autoantibody response of systemic lupus erythematosus.

Abstract

A strong gene interaction between HLA-DQ1 and DQ2 alleles has been associated with anti-Ro/SSA autoantibodies ( HLA-DQ1/DQ2 heterozygotes is most closely related to antiRo/SSA autoantibodies, thereby supporting a gene complementation mechanism. Beyond this effect, an RFLP associated with HLA-DQ2 and/or DR7 is also related to Ro/SSA precipitins. Multiple molecular histocompatibility mechanisms are implicated, therefore, in the production of anti-Ro/SSA autoantibodies in autoimmune disease. For anti-Ro/SSA autoantibodies in SLE, and perhaps more generally, these data show that the histocompatibility antigens are among the elements that confer autoimmune response specificity and restrict the production of particular autoantibodies among patients with systemic lupus erythematosus. (J. Clin. Invest. 1990. 86:606-611.)

Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus.

“…In addition, vesicular stomatitis virus, through its G protein, is known to be capable of generating HLA class II restricted T-lymphocyte responses (33). This is compatible with the known HLA class II and T-lymphocyte receptor associations with the anti-Ro/SSA autoimmune response (1,(3)(4)(5).…”

“…The presence of anti-Ro/SSA autoantibodies is associated with powerful genetic effects at the HLA-DQ and the T-cell receptor f chain genes (3)(4)(5). These results, along with the greater antigenicity of the human form of Ro/SSA (6), implicate the particular human Ro/SSA autoantigen, histocompatibility molecules, and T-cell receptors in the molecular control of this autoimmune response.…”

Association of antiphosphatidylserine/prothrombin autoantibodies with HLA class II genes

“…HLA associations with SLE and autoantibodies found in SLE have been investigated extensively in many ethnic groups. Anti-Ro/SSA antibodies have been associated with DQ1/DQ2 alleles (21) and genotypes associated with them (22)(23)(24). Anti-La/SSB have been associated with HLA-DR3, and RNP (Sm) with HLA-DR4 (25).…”

Sjögren’s Syndrome: Autoantibodies to Cellular Antigens

“…A strong gene interaction between HLA-DQ1 and -DQ2 alleles has been associated with higher levels of anti-Ro/SSA and anti-La/ SSB antibodies in patients with SS [67]. In a subsequent study of Fujisaku et al [68], restriction fragment length polymorphisms of the DQa and DQß genes have been related to Ro/SSA precipitins in patients with SLE suggesting a gene complementation mechanism involved in the generation of the autoimmune response. In another study, Reveille et al [69] found that almost all of the antiRo/SSA patients had a glutamine at amino acid sequence position 34 of a DQA1 chain and a leucine at position 26 of DQB1 chain.…”