Human leucocyte antigen class II associations in chronic idiopathic urticaria

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases, Recent investigations have shown about 30% of patients with chro nic idiopathic urticaria (CIU) have IgG autoantibodies against the high-aff inity IgE receptor, Fc epsilon RI, or IgE, A link between MHC class II alle les and CIU has not been reported previously, DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined us ing the polymerase chain reaction with sequence-specific primers, testing f or DRB and DQB1 alleles. The frequency of alleles in CIU patients was compa red with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intrade rmal injection of autologous serum and their serum-induced histamine releas e from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 ( DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10(-5) and P = 2 x 10(-4), res pectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), ar e significantly less frequently associated with CIU, The HLA DRB1*04 associ ation is particularly strong (corrected P = 3.6 x 10(-6)) for patients whos e serum has in vivo and in vitro histamine-releasing activity, HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.