INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, University of Lorraine, Nancy, France.
Oasi Research Institute-IRCCS, Troina, Italy.
Allergy. 2022 Jun;77(6):1827-1834. doi: 10.1111/all.15147. Epub 2021 Nov 14.
Nonimmediate (delayed)-allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci.
Using next-generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls.
The two alleles DRB302:02:01:02 and DRB302:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37-23.32; p < .0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838 genetic variants of the HLA-DRB3 genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06-1.92; p = .001), but not immediate hypersensitivity.
We showed that the HLA-DRB3 locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of HLA-DRB3*02:02 alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins.
青霉素的非即刻（迟发）过敏反应很常见，其中一些可能危及生命。影响这些反应的遗传因素尚不清楚/知之甚少/理解不足。我们评估了涵盖 HLA 基因座的青霉素迟发过敏的遗传预测因子。
使用下一代测序（NGS），我们对 24 例迟发性超敏反应患者和 20 例意大利已确诊的青霉素即刻超敏反应患者的 MHC 区域进行了基因分型。随后，我们对 98 例西班牙迟发性超敏反应患者和 315 例即刻超敏反应患者与 1308 例对照的 Illumina Immunochip 基因分型数据进行了分析，这些数据涵盖了 HLA 基因座。
在 20 例迟发性反应患者（83%）和 10 例即刻反应患者（50%）中报告了两个等位基因 DRB302:02:01:02 和 DRB302:02:01:01，但在Allele Frequency Net Database 中未报告。与即刻反应相比，携带至少一个这两个等位基因会增加迟发性反应的风险，比值比为 8.88（95%CI，3.37-23.32；p<.0001）。HLA-DRB3 基因座的 rs9268835、rs6923504、rs6903608 和 rs9268838 遗传变异的（ACAA）单倍型与青霉素迟发性过敏的风险增加显著相关（比值比，1.7；95%CI：1.06-1.92；p=0.001），但与即刻过敏无关。
我们表明，HLA-DRB3 基因座与青霉素迟发性过敏反应的风险增加密切相关，至少在西南欧是如此。在不同来源的更大人群样本中进一步评估 HLA-DRB3*02:02 等位基因在严重青霉素迟发性过敏反应风险管理中的作用。
