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 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.
Sánchez-Velasco
Pablo
P
Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Antón
Encarnación
E
Muñoz
Daniel
D
Martínez-Quesada
Jorge
J
Ruíz de Alegría
Carlos
C
López-Hoyos
Marcos
M
García-Martín
Alfredo
A
Jiménez
Isabel
I
Alonso
Sofía T
ST
Duque
Soledad
S
Suárez
Alicia
A
Jerez
Juan
J
Leyva-Cobián
Francisco
F
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
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