Differential contribution of HLA-DR, DQ, and TAP2 alleles to systemic lupus erythematosus susceptibility in Spanish patients:: role of TAP2*01 alleles in Ro autoantibody production

Objective-To study the influence MHC class II and TAP2 alleles exert on systemic lupus erythematosus (SLE) susceptibility and on the clinical and serological manifestations of the disease, in a cohort of Spanish patients. Methods-HLA-DR serological typing and HLA-DQA, DQB, and TAP2 DNA sequence specific oligotyping, were carried out in 85 unrelated Spanish SLE patients and 186 healthy controls. Autoantibodies detection was carried out by indirect immunofluorescence and counter immune electrophoresis. Results-Total SLE group: the frequency of HLA-DR3 and HLA-DQA1 star 0501 is significantly increased in this group (p(c)<0.005, delta=0.34 and p(c)<0.005, delta= 0.45, respectively) although the highest delta value (delta=0.87) is obtained when the TAP2 star 01 alleles are considered. No DQB allele shows significant deviation from the control group. Renal damage: it mainly occurs in HLA-DR3 patients (p(c)<0.0005 and delta=0.72). HLA-DQA1 star 0501 (p(c)<0.05, delta=0.57) and DQB1 star 0201 (p(c) NS, delta=0.56) are weaker susceptibility factors. Ro+ (but not La) group: this autoantibody response is associated with TAP2 star 01 alleles in homozygosity (p<0.05, delta=0.81). Ro/La+ group: it has a different genetic background as HLA-DQA1 star 0501 (delta=1) and HLA-DQB1 star 0201 (delta=1) are the main susceptibility factors. Conclusions-A differential association between HLA-DR, DQA1, and DQB1 alleles and SLE or its clinical and serological manifestations are found. Furthermore, the associations are different to the ones reported in other ethnic groups. Finally, TAP2 star 01 group of alleles are associated with the highest susceptibility to SLE (higher than HLA-DR3) and may influence Ho (but not La) autoantibodies production, whereas HLA-DQA1 star 0501 and DQB1 star 0201 mediates concomitant Ro and La production.