Cheng Ting, Zhang He-Yi, Wang Tian-Run, Li Ruo-Lan, Jing Zhi-Nan, Huo Yue-Hong, Zhang Sheng-Xiao
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Shanxi Provincial Key Laboratory of Rheumatism Immune Microecology, Taiyuan, Shanxi Province, China.
Sci Rep. 2025 Jul 2;15(1):22722. doi: 10.1038/s41598-025-08361-z.
This study uses Mendelian randomization (MR) to investigate the potential causal relationships between viral infections, including Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), SARS-CoV-2, cytomegalovirus (CMV), human herpes virus 6 (HHV-6), varicella-zoster virus (VZV), herpes simplex virus (HSV), influenza A virus, and hepatitis B virus, and the risk of systemic sclerosis (SSc). Summary-level data on viral exposures and SSc outcomes were obtained from public genome-wide association studies (GWAS) databases. Causality was assessed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted to enhance the reliability and robustness of our findings. Genetically predicted anti-EBV viral capsid antigen IgG levels (OR = 3.400, 95% CI = 1.093-10.571, p = 0.035) were causally associated with an elevated risk of SSc, while HIV (OR = 0.787, 95% CI = 0.629-0.985, p = 0.037) and SARS-CoV-2 (OR = 0.335, 95% CI = 0.116-0.964, p = 0.043) correlated with a reduced risk of SSc. Sensitivity analysis validated the robustness of these associations (p > 0.05). Further elucidation of the underlying mechanisms by which EBV increases the risk of SSc could potentially identify interventions for promoting SSc prevention.
本研究采用孟德尔随机化（MR）方法，调查包括爱泼斯坦 - 巴尔病毒（EBV）、人类免疫缺陷病毒（HIV）、严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、巨细胞病毒（CMV）、人类疱疹病毒6型（HHV-6）、水痘 - 带状疱疹病毒（VZV）、单纯疱疹病毒（HSV）、甲型流感病毒和乙型肝炎病毒在内的病毒感染与系统性硬化症（SSc）风险之间的潜在因果关系。病毒暴露和SSc结局的汇总水平数据来自公开的全基因组关联研究（GWAS）数据库。使用逆方差加权（IVW）、MR-Egger和加权中位数方法评估因果关系。进行敏感性分析以提高我们研究结果的可靠性和稳健性。基因预测的抗EBV病毒衣壳抗原IgG水平（OR = 3.400，95%CI = 1.093 - 10.571，p = 0.035）与SSc风险升高存在因果关联，而HIV（OR = 0.787，95%CI = 0.629 - 0.985，p = 0.037）和SARS-CoV-2（OR = 0.335，95%CI = 0.116 - 0.964，p = 0.043）与SSc风险降低相关。敏感性分析验证了这些关联的稳健性（p>0.05）。进一步阐明EBV增加SSc风险的潜在机制可能有助于确定促进SSc预防的干预措施。
