Supplementary Material for: Two Novel Human Leukocyte Antigen Alleles Are Associated with Decreased Risk of Onychomycosis in a Large Cohort of Danish Blood Donors

<b><i>Introduction:</i></b> Antigen presentation and antimicrobial immune responses involve the human leukocyte antigen (HLA) system. Onychomycosis is primarily caused by dermatophytes and affects around 5.5% of the population worldwide. Yet, only limited data exist on the associations between the HLA system and onychomycosis. Thus, the objective of the study was to investigate if there is an association between HLA alleles and onychomycosis. <b><i>Methods:</i></b> Participants in the Danish Blood Donor Study were defined as cases of onychomycosis and controls based on antifungal prescriptions in the national prescription registry. Associations were investigated using logistic regressions adjusted for confounders and were Bonferroni corrected for multiple tests. <b><i>Results:</i></b> A total of 3,665 participants were considered onychomycosis cases, and 24,144 participants were considered controls. We found two protective HLA alleles of onychomycosis: DQB1*06:04, odds ratios (OR) 0.80 (95% confidence interval (CI) 0.71–0.90), and DRB1*13:02, OR 0.79 (95% CI: 0.71–0.89). <b><i>Conclusion:</i></b> The finding of two novel protective alleles of onychomycosis indicates that certain HLA alleles have certain antigen presentation properties affecting the risk of fungal infection. These findings may provide the basis for future research identifying immunologically relevant antigens of fungi causing onychomycosis, which could ultimately lead to targets of new drugs with antifungal effects.

<b><i>引言:</i></b> 抗原呈递与抗菌免疫应答均涉及人类白细胞抗原（human leukocyte antigen，HLA）系统。甲真菌病（onychomycosis）主要由皮肤癣菌引起，全球约5.5%的人群受其困扰。然而，目前关于HLA系统与甲真菌病之间关联的研究数据仍较为有限。本研究旨在探究HLA等位基因与甲真菌病是否存在相关性。<b><i>方法:</i></b> 本研究以丹麦献血者研究（Danish Blood Donor Study）的参与者为研究对象，基于国家处方登记库中的抗真菌处方信息，将其划分为甲真菌病病例组与对照组。采用校正混杂因素的逻辑回归分析关联情况，并通过邦费罗尼校正处理多重检验问题。<b><i>结果:</i></b> 本研究共纳入3665名甲真菌病病例参与者与24144名对照参与者。本研究发现两种与甲真菌病相关的保护性HLA等位基因：DQB1*06:04（比值比（odds ratios，OR）=0.80，95%置信区间（confidence interval，CI）：0.71~0.90）以及DRB1*13:02（OR=0.79，95%CI：0.71~0.89）。<b><i>结论:</i></b> 本研究发现的两种甲真菌病保护性新等位基因提示，部分HLA等位基因具备特定的抗原呈递特性，可影响真菌感染风险。上述研究结果可为后续研究提供基础，助力鉴定引发甲真菌病的真菌免疫学相关抗原，最终有望开发出具有抗真菌作用的新型药物靶点。