Deterioration of connectin/titin and nebulin filaments by an excess of protease inhibitors

OBJECTIVE: To investigate HLA class II allele associations with autoantibody responses to Ro/SS-A and La/SS-B among Japanese subjects. METHODS: Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A and/or La/SS-B. RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 chain. HLA class II allele distributions did not differ among 3 anti-Ro/SS-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sj?gren's syndrome, and women with no apparent symptoms of rheumatic disease. CONCLUSION: HLA class II allele distributions differ among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. Our findings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.