Sensitivity to Bee Venom Antigen Phospholipase A 2: Association With Specific HLA Class I and Class II Alleles and Haplotypes in Beekeepers and Allergic Patients

Abstract

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 A 2 (vbPLA 2) 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 vbPLA 2 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 vbPLA 2 hypersensitivity, at least in our region.