Association of clinical manifestations with HLA-B alleles in Takayasu arteritis

Abstract

HLA-DNA typing using PCR-SSOP and PCR-DCP methods was performed in 85 patients with Takayasu arteritis and 492 healthy controls who had been typed for HLA by serological method. Frequencies of HLA-B52 (B∗5201) and B39 (B∗3901 and B∗3902) were significantly increased in the patients. Frequency of HLA-DRB1∗1502 was also increased but it was suggested to be a reflection of its linkage disequilibrium with B52. Association of HLA-B52 and B39 with seven clinical manifestations – pulmonary infarction, ischemic heart disease, aortic regurgitation, systemic hypertension, renal artery stenosis, cerebrovascular disease, and visual disturbance – in 132 HLA-typed patients with Takayasu arteritis was studied. In HLA-B52 positive TA patients, aortic regurgitation (vs B52(−)-B39(+), OR=3.8, P<0.05, vs B52(−)-B39(−), OR=5.49, P<0.001), ischemic heart disease (vs B52(−)-B39(+), OR=12.05, P<0.05, vs B52(−)-B39(−), OR=2.85, P<0.05), and pulmonary infarction (vs B52(−)-B39(+), OR=5.74, P<0.03) were found to be significantly prevalent. On the other hand, in HLA-B39 positive TA patients, frequency of renal artery stenosis was significantly increased (vs B52(+)-B39(−), OR=12.14, P<0.001, vs B52(−)-B39(−), OR=5.21, P<0.03). These observations have suggested that HLA-B52 molecule and B39 molecule would contribute to different clinical manifestations by binding different antigenic peptides to cause inflammations. Thus HLA-B molecule may play an important role in pathogenesis or determining clinical manifestations of Takayasu arteritis.