LEUKOCYTE ANTIGEN-DQB1-ASTERISK-03 ALLELES ARE ASSOCIATED WITH ALOPECIA-AREATA

Alopecia areata (AA) is characterized by hair loss in patches (patchy AA), over the entire scalp (AT, totalis), or universally (AU). An auto immune mechanism has been hypothesized, because the inflammatory infil trate targeted to the hair follicles includes activated T cells. To in vestigate whether or not genetic polymorphism of the human leukocyte a ntigen (HLA) region contributes to disease susceptibility, we used seq uence-specific oligonucleotides and amplified genomic DNA to define HL A-DQA1, -DQB1, and -DPB1 alleles in a cohort of 85 white patients. The frequency of DQB1()0301 was significantly increased to 41% in all pa tients, and to 47% in AT/AU patients relative to controls (27%). Analy zed together, DQB1()03 alleles (DQB1(*)0301-(*)0303) were increased t o 80% (all patients) and to 92% AT/AU) (odds ratio = .12.14, p = 0.000 03, corrected. This striking association implicates the DQB1()03 alle les in the pathogenesis of AA. DQB1()06 was decreased relative to con trols (56%) in all patients (32%, odds ratio = 0.37, p = 0.0045, corre cted). An increase was observed in the HLA-DRB111(DR5) allele DRB1(*) 1104, which may result from linkage disequilibrium with DQB1 alleles. Sequence comparison among the allele products associated with AA indic ates that the DQB1()03 alleles carry a unique proline at position 55 that is not present in alleles that are neutral or negatively associat ed may exert considerable control over immune responsiveness and the i nitiation or persistence of a T-cell autoimmune response against the h air follicle.