Faux J A, Moffatt M F, Lalvani A, Dekker J, Warrell D A, Cookson W O
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK.
Clin Exp Allergy. 1997 May;27(5):578-83.
Stings from bees and wasps can cause systemic reactions which can be fatal in some individuals. In these venom-sensitive patients, specific IgE to the venom is produced and is considered to participate in the adverse reactions. This immune response requires antigen presentation by human leucocyte antigens (HLA) class II molecules, which includes DR and DP, which are present on antigen presenting cells.
To test for associations between HLA class II DRB1 and DPB1 alleles and life-threatening sensitivity to both bee and wasp venoms. To establish further whether any associations are independent of the atopy phenotype.
A total of 33 bee- and 44 wasp-venom-sensitive patients was studied. DRB1 genotypes were determined by single stranded oligonucleotide (SSO) probing of PCR products, and DPB1 genotypes by amplified fragment length polymorphism (AFLP) analysis. Total and specific IgE were measured using the Pharmacia Immunocap, FEIA. Patients with specific IgE to the venom antigens only were termed monosensitive and those with additional specific IgE to HDM and/or GP were termed polysensitive.
Allele frequencies were compared to an unrelated control population. The 33 bee-sensitive patients had a greater prevalence of DRB107 alleles than the control subjects, 26% vs 14%, with an odds ratio (OR) of 2.1 (95% CI, 1.2-3.7, P = 0.015, corrected for multiple comparisons, Pc = ns). This association was confined to the 15 monosensitive bee patients, who had a 43% DRB107 allele frequency when compared with 11% in the 18 polysensitive bee patients, OR 6.1 (95% CI, 1.73-22, P = 0.004, Pc = 0.05), and when compared with a control group of non-venom subjects, 43% vs 16%, OR 3.9 (95% CI, 1.72-9.0, P = 0.002, Pc = 0.02). The 44 wasp-sensitive patients had an increase in the DRB111 allele when compared with the control subjects, 13% vs 6%, with an OR 2.2 (95% CI, 1.0-4.6, P = 0.04, Pc = NS), and a decreased prevalence of DRB104 alleles, 10% vs 19%, with an OR 0.33 (95% CI, 0.24-0.99, P = 0.04, Pc = NS), but these were not significant when multiple comparisons were taken into account. The DPB1 alleles were not significantly different between the venom sensitive patients and the controls.
Patients monosensitive to bee venom had a significantly greater prevalence of DRB107 alleles than the non-venom, control population suggesting that IgE responses in these patients may, in part be controlled by immune response HLA class II genes. These results are also suggestive of wasp-sensitive patients having a higher prevalence of DRB111 and a lower prevalence of DRB1*04 than the control population.
蜜蜂和黄蜂蜇伤可引发全身反应，在某些个体中可能致命。在这些对毒液敏感的患者中，会产生针对毒液的特异性IgE，并被认为参与了不良反应。这种免疫反应需要人类白细胞抗原（HLA）II类分子呈递抗原，其中包括存在于抗原呈递细胞上的DR和DP。
检测HLA II类DRB1和DPB1等位基因与对蜜蜂和黄蜂毒液的危及生命的敏感性之间的关联。进一步确定任何关联是否独立于特应性表型。
共研究了33例对蜜蜂毒液敏感和44例对黄蜂毒液敏感的患者。通过对PCR产物进行单链寡核苷酸（SSO）探针检测来确定DRB1基因型，通过扩增片段长度多态性（AFLP）分析来确定DPB1基因型。使用Pharmacia Immunocap FEIA检测总IgE和特异性IgE。仅对毒液抗原有特异性IgE的患者称为单敏感患者，对屋尘螨和/或草花粉有额外特异性IgE的患者称为多敏感患者。
将等位基因频率与无关对照人群进行比较。33例对蜜蜂毒液敏感的患者中DRB107等位基因的患病率高于对照受试者，分别为26%和14%，优势比（OR）为2.1（95%可信区间，1.2 - 3.7，P = 0.015，经多重比较校正，Pc =无显著性差异）。这种关联仅限于15名单敏感蜜蜂患者，他们的DRB107等位基因频率为43%，而18例多敏感蜜蜂患者为11%，OR为6.1（95%可信区间，1.73 - 22，P = 0.004，Pc = 0.05），与非毒液对照受试者组相比，分别为43%和16%，OR为3.9（95%可信区间，1.72 - 9.0，P = 0.002，Pc = 0.02）。44例对黄蜂毒液敏感的患者与对照受试者相比，DRB111等位基因增加，分别为13%和6%，OR为2.2（95%可信区间，1.0 - 4.6，P = 0.04，Pc =无显著性差异），DRB104等位基因患病率降低，分别为10%和19%，OR为0.33（95%可信区间，0.24 - 0.99，P = 0.04，Pc =无显著性差异），但考虑多重比较时这些差异无统计学意义。毒液敏感患者与对照之间的DPB1等位基因无显著差异。
对蜜蜂毒液单敏感的患者中DRB107等位基因的患病率显著高于非毒液对照人群，表明这些患者中的IgE反应可能部分受免疫反应HLA II类基因控制。这些结果还提示，对黄蜂毒液敏感的患者中DRB111的患病率高于对照人群，而DRB1*04的患病率低于对照人群。
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