Department of Dermatology, Zealand University Hospital Roskilde, Sygehusvej 5, 4000, Roskilde, Denmark.
Department of Clinical Immunology, Zealand University Hospital, Køge, Denmark.
Arch Dermatol Res. 2023 May;315(4):895-902. doi: 10.1007/s00403-022-02454-9. Epub 2022 Nov 17.
The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD.
Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests.
A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B57:01, OR 1.19 (95% CI: 1.09-1.31), C01:02, OR 1.19 (95% CI: 1.08-1.32), C06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB101:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB102:01, OR 0.89 (95% CI: 0.85-0.94), and DRB103:01, OR 0.89 (95% CI: 0.85-0.94).
Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles.
人类白细胞抗原系统(HLA)分为两类,参与抗原呈递:I 类呈递细胞内抗原,II 类呈递细胞外抗原。虽然感染易感性与 HLA 系统相关,但关于 HLA 基因型与马拉色菌相关皮肤疾病(MRSD)之间的关联的数据尚缺乏。因此,本研究的目的是探讨 HLA 等位基因与 MRSD 之间的关联。
丹麦献血者研究(2010-2018 年)的参与者提供了关于生活方式、人体测量学测量和已填处方登记数据的问卷数据。使用 Illumina Infinium Global Screening Array 进行基因分型,并使用 HIBAG 算法进行 HLA 等位基因推断。病例和对照通过外用酮康唑 2%的处方定义为 MRSD 的替代物。使用逻辑回归评估 HLA 等位基因与 MRSD 之间的关联,调整混杂因素,并对多次检验进行 Bonferroni 校正。
共有 9455 名参与者被认为是 MRSD 病例,24144 名参与者被认为是对照。我们确定了四个风险等位基因 B57:01,比值比(OR)为 1.19(95%可信区间:1.09-1.31),C01:02,OR 为 1.19(95%可信区间:1.08-1.32),C06:02,OR 为 1.14(95%可信区间:1.08-1.22)和 DRB101:01,OR 为 1.10(95%可信区间:1.04-1.17),以及两个保护性等位基因 DQB102:01,OR 为 0.89(95%可信区间:0.85-0.94)和 DRB103:01,OR 为 0.89(95%可信区间:0.85-0.94)。
在我们的队列中,确定了五个与 HLA 等位基因与 MRSD 之间的新关联,一个先前的关联得到了证实。未来的研究应评估马拉色菌抗原与相关 HLA 等位基因的抗原结合特性之间的相关性。