title: Sensitivity to bee venom antigen phospholipase A2: 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 A2 (vbPLA2) is significantly associated with the presence of susceptible HLA class II alleles: DRB1*0101 (RR = 2.7, p < 3 x 10(-3)), DRB1*0103 (RR = 21.2, p < 7.5 x 10(-11)), DQA1*0101 (RR = 1.2, p < 38.52 x 10(-10)), and DQB1*0501 (RR = 4, p < 2.18 x 10(-10)). Some HLA class I alleles were also associated with risk to bee venom allergy: A*01 (RR = 2.4, p < 7.5 x 10(-4)), B*57 (RR = 35.1, p < 3.5 x 10(-7)), and B*5901 (p < 3.5 x 10(-5)), but they are probably of secondary significance. Three- (DRB1*0103-DQA1*0101-DQB1*0501) (RR = 21.24, p < 7.5 x 10(-11)) and five-loci (A*01-B*59-DRB1*0103-DQA1*0101-DQB1*0501) (p < 2.3 x 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 x 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.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sánchez-Velasco
authors.forename: Encarnación
authors.initials: E
authors.lastname: Antón
authors.forename: Daniel
authors.initials: D
authors.lastname: Muñoz
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez-Quesada
authors.forename: Carlos
authors.initials: C
authors.lastname: Ruíz de Alegría
authors.forename: Marcos
authors.initials: M
authors.lastname: López-Hoyos
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Martín
authors.forename: Isabel
authors.initials: I
authors.lastname: Jiménez
authors.forename: Sofía T
authors.initials: ST
authors.lastname: Alonso
authors.forename: Soledad
authors.initials: S
authors.lastname: Duque
authors.forename: Alicia
authors.initials: A
authors.lastname: Suárez
authors.forename: Juan
authors.initials: J
authors.lastname: Jerez
authors.forename: Francisco
authors.initials: F
authors.lastname: Leyva-Cobián
mesh_terms: D001514:Bee Venoms / Q000276:immunology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D016013:Likelihood Functions; D008297:Male; D010641:Phenotype; D010741:Phospholipases A / Q000276:immunology*; D054467:Phospholipases A2; D013030:Spain
chemical_list: D001514:Bee Venoms; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010741:Phospholipases A; D054467:Phospholipases A2