Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Internal Diseases Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Iran J Allergy Asthma Immunol. 2021 Feb 11;20(1):67-75. doi: 10.18502/ijaai.v20i1.5413.
Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients. We observed the positive associations of DRB107 and DRB107-DQB102 haplotypes with articular and pulmonary involvement (p=0.006 and p<0.001 respectively), DRB103 and DQB102 alleles, and DRB103-DQB102 haplotypes with cutaneous (p=0.03, p=0.004 and p=0.02 respectively) and renal involvement, and DRB113 as well as DRB113-DQB106 haplotypes with renal involvement. Conversely, negative associations of DRB113 with cutaneous and gastrointestinal disorders (p=0.004 and p=0.02 respectively) and DRB101 with renal involvement (p=0.03) were found in our patients. Patients carrying susceptible HLA-DRB1 alleles had a higher risk for expression of cutaneous involvement (p=0.03), anti-coagulant antibody development (p=0.01), and a lower risk for pulmonary disorders compared to patients' negatives for susceptible alleles (p=0.04). Our findings on associations between HLA risk allele (DRB103) as well as non-risk alleles with particular clinical manifestations and between the potentially protective allele (DRB101) and protection against renal involvement indicate the important role of HLA class II genes in predisposing of specific serological and clinical features of SLE disease which could be implicative for therapeutic applications and better management of SLE patients.
鉴于遗传风险因素与系统性红斑狼疮（SLE）的临床特征之间存在潜在联系，本研究旨在探讨伊朗一组 SLE 患者中人类白细胞抗原（HLA）-DRB1/DQB1 等位基因和单倍型与疾病临床亚型之间的关系。在 127 例 SLE 患者和 153 名匹配的健康对照中，通过 PCR-SSP 确定了 HLA-DRB1 和 HLA-DQB1 等位基因。在患者中分析了各种临床表现与 HLA 等位基因/单倍型的关系。我们观察到 DRB107 和 DRB107-DQB102 单倍型与关节和肺部受累呈正相关（p=0.006 和 p<0.001），DRB103 和 DQB102 等位基因，以及 DRB103-DQB102 单倍型与皮肤（p=0.03、p=0.004 和 p=0.02）和肾脏受累有关，DRB113 以及 DRB113-DQB106 单倍型与肾脏受累有关。相反，在我们的患者中，DRB113 与皮肤和胃肠道疾病呈负相关（p=0.004 和 p=0.02），DRB101 与肾脏受累呈负相关（p=0.03）。与 HLA 易感等位基因阴性的患者相比，携带易感 HLA-DRB1 等位基因的患者皮肤受累（p=0.03）、抗凝抗体发育（p=0.01）的风险更高，而肺部疾病的风险更低（p=0.04）。我们发现 HLA 风险等位基因（DRB103）以及非风险等位基因与特定临床表现之间的关联，以及潜在保护等位基因（DRB101）与肾脏受累的保护作用之间的关联，表明 HLA Ⅱ类基因在易患特定血清学和临床特征方面的重要作用SLE 疾病，这可能对治疗应用和 SLE 患者的更好管理具有启示意义。
