Contrasting molecular patterns of MHC class II alleles associated with the anti-Sm and anti-RNP precipitin autoantibodies in systemic lupus erythematosus.

OBJECTIVE

To find evidence of a potential genetic predisposition to the anti-Sm or anti-RNP precipitin autoantibody responses.

METHODS

HLA-DR and DQ alleles determined by restriction fragment length polymorphism and/or oligotyping in 49 subjects with either anti-Sm alone or anti-RNP alone were compared with those in 139 race-matched normal control subjects and 59 race-matched lupus patients without anti-Sm and anti-RNP autoantibodies.

RESULTS

Black patients with anti-Sm precipitin had increased frequencies of HLA-DR2 and the DQw6-associated DQA10102 (P = 0.007, odds ratio [OR] = 6.7) and DQB10602 (P = 0.001, OR = 9.1) chain alleles compared with normal black control subjects. Black patients with anti-RNP precipitin showed significant increases in the DQw5-associated DQA10101 (P = 0.03, OR = 5.5) and DQB10501 (P = 0.002, OR = 23.3) chain alleles compared with lupus patients without anti-Sm or RNP. While patients with anti-RNP precipitin showed an increased frequency of the DQw8-associated allele DQB10302 (P = 0.02, OR = 3.7) compared with normal controls, as well as an increased frequency of the DQw5-associated alleles DQA10101 and DQB1*0501 (P = 0.05, OR = 4.2) compared with lupus patients without anti-Sm or RNP. There were no specific HLA-DR2 or DR4 subtype associations found with either anti-Sm or RNP precipitin autoantibodies.

CONCLUSION

There are distinct patterns of major histocompatibility complex class II allele associations with the anti-Sm versus the anti-RNP precipitin autoantibody responses, and HLA-DQ associations may be more primary than HLA-DR associations.