PEMPHIGUS-VULGARIS AUTOANTIBODY RESPONSE IS LINKED TO HLA-DQB1-ASTERISK-0503 IN PAKISTANI PATIENTS

Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucou s membranes characterized by an autoantibody response against an epide rmal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hyb ridization. The results were compared with two separate ethnically mat ched control populations. We found that PV patients from Pakistan had significantly increased frequencies of DRB11404 (P = 0.01), DQA1*0101 (P = 0.02), and DQB10503 (P = 0.01). Among the patients of non-Jewis h European ancestry, DRB11401 (P < 10(-6)) DQA1*0101 (P < 10(-5)) and DQB10503 (P < 10(-6)), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV anti body was performed in 67 relatives of the 19 Pakistani patients. The r esults showed strong evidence for linkage of HLA-DRB11404, DQA1*0101, DQB10503, with the presence of PV antibody in relatives' families wi th a significant logarithm of the odds score of 6.06. Based on the thr ee dimensional structure of class II molecules, we propose that HLA-DQ A10101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with suscep tibility to PV in non-Jewish populations. (C) American Society for His tocompatibility and Immunogenetics, 1997. Published by Elsevier Scienc e Inc.