Sensitivity to Bee Venom Antigen Phospholipase A2: Association With Specific HLA Class I and Class II Alleles and Haplotypes in Beekeepers and Allergic Patients

Bee venom hypersensitivity is a clinical entity of outstanding importance because bee stings are a leading cause of mortality worldwide. Individuals with immediate-type bee venom hypersensitivity, beekeepers, and healthy controls were examined for HLA-DRB1, DQB1, and DQA1 alleles by sequence-specific oligonucleotide probe typing. Defined hypersensitivity to bee venom antigen phospholipase A2 (vbPLA2) is significantly associated with the presence of susceptible HLA class II alleles: DRB1*0101 (RR = 2.7, p < 3 × 10−3), DRB1*0103 (RR = 21.2, p < 7.5 × 10−11), DQA1*0101 (RR = 1.2, p < 38.52 × 10−10), and DQB1*0501 (RR = 4, p < 2.18 × 10−10). Some HLA class I alleles were also associated with risk to bee venom allergy: A*01 (RR = 2.4, p < 7.5 × 10−4), B*57 (RR = 35.1, p < 3.5 × 10−7), and B*5901 (p < 3.5 × 10−5), but they are probably of secondary significance. Three- (DRB1*0103-DQA1*0101-DQB1*0501) (RR = 21.24, p < 7.5 × 10−11) and five-loci (A*01-B*59-DRB1*0103-DQA1*0101-DQB1*0501) (p < 2.3 × 10−6) extended haplotypes are also significantly carried by vbPLA2 allergic patients. When HLA allele frequencies from patients are compared with those from beekeepers, only HLA-DRB1*0103 (RR = 11.7, p < 8.5 × 10−5) and HLA-DQA1*0101 (p < 0.02) were significantly increased in the former. These observations emphasize the importance of the DRB1*0103-DQA1*0101-DQB1*0501 haplotype as a strong candidate for susceptibility to vbPLA2 hypersensitivity, at least in our region.