Human leukocyte antigen-DQB1*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 autoimmune mechanism has been hypothesized, because the inflammatory infiltrate targeted to the hair follicles includes activated T cells. To investigate whether or not genetic polymorphism of the human leukocyte antigen (HLA) region contributes to disease susceptibility, we used sequence-specific oligonucleotides and amplified genomic DNA to define HLA-DQA1, -DQB1, and -DPB1 alleles in a cohort of 85 white patients. The frequency of DQB1*0301 was significantly increased to 41% in all patients, and to 47% in AT/AU patients relative to controls (27%). Analyzed together, DQB1*03 alleles (DQB1*0301-*0303) were increased to 80% (all patients) and to 92% (AT/AU) (odds ratio = 12.14, p = 0.00003, corrected). This striking association implicates the DQB1*03 alleles in the pathogenesis of AA. DQB1*06 was decreased relative to controls (56%) in all patients (32%, odds ratio = 0.37, p = 0.0045, corrected). An increase was observed in the HLA-DRB1*11(DR5) allele DRB1*1104, which may result from linkage disequilibrium with DQB1 alleles. Sequence comparison among the allele products associated with AA indicates that the DQB1*03 alleles carry a unique proline at position 55 that is not present in alleles that are neutral or negatively associated with the disease. This highly significant association may exert considerable control over immune responsiveness and the initiation or persistence of a T-cell autoimmune response against the hair follicle.