Association of Infectious Mononucleosis with Risk of Subsequent Autoimmune Diseases: A Nationwide Population-Based Cohort Study

傳染性單核球增多症（人類疱疹病毒第四型感染）與罹患自體免疫疾病風險性的相關性：以全國人口為對象之世代研究

李向嚴(Hsiang-Yen Lee) ； 張晉魁(Ching-Kuei Chang) ； 林子閔(Tzu-Min Lin) ； 郭芷彤(Tzu-Tung Kuo) ； 陳錦華(Jin-Hua Chen) ； 甄沛勤(Pei-Chin Chen) ； 張棋楨(Chi-Ching Chang)

《Formosan Journal of Rheumatology》 36卷2期 (2022/12) Pp. 44-55

https://doi.org/10.6313/FJR.202212_36(2).0006

摘要

Objective: Infectious agents can trigger autoimmune responses in several chronic inflammatory diseases. This study investigated the association of infectious mononucleosis (IM), predominantly caused by Epstein-Barr virus (EBV), with the risk of autoimmune diseases (ADs). Method: We used claims data from Taiwan's National Health Insurance Research Database to determine the incidence of ADs with or without a diagnosis of IM from 2006 to 2017. Incidence rate ratios and hazard ratios (HRs) of ADs for IM were estimated using Cox's proportional hazard regression model. Results: The overall incidence of ADs was higher in the IM group than in the control cohort (274.84 vs. 66.34 per 100,000 person-years; incidence rate ratio, 4.14; 95% confidence interval [CI], 3.24-5.30), with an adjusted hazard ratio (aHR) of 6.23 (95% CI, 4.83-8.21). Compared with the control group, the IM group had higher aHRs for incident systemic ADs such as rheumatoid arthritis (aHR, 4.52; 95% CI, 1.21-17.58), systemic lupus erythematosus (aHR, 13.58; CI, 6.32-37.81), and systemic vasculitis (aHR, 5.93; 95% CI, 1.89-18.17). Furthermore, the aHR of the IM group was significantly higher for incident nine types of organ-specific ADs. Conclusion: IM is a risk factor for ADs, implying the importance of EBV infection in the development of ADs. Further mechanistic research is needed.

關鍵字

Epstein-Barr virus ； infectious mononucleosis ； autoimmune disease ； nationwide population-based cohort study

並列摘要

目的：傳染病原體可以在幾種慢性發炎疾病中觸發自身免疫反應。本次研究的目的是調查傳染性單核球增多症（IM），這種多由人類疱疹病毒第四型（EBV）感染造成疾病與罹患自身免疫性疾病風險之間的關係。方法：本篇使用臺灣國家健康保險研究資料庫的保險索引資料，資料範圍為2006－2017年，匯出包含有傳染性單核球增多症診斷碼與否的自身免疫性疾病（AD）發病率。用Cox's proportional hazard regression model估計了傳染性單核球增多症（主因EBV感染）與AD的發病率和風險比（HR）。結果：曾有IM病史群體的自體免疫疾病總發病率高於非IM病史群體（每10萬人年274.84比66.34；發病率為（4.14，95％CI 3.24－5.30），調整後的HR為6.23（95％CI 4.83－8.21）。與非IM病史群體相比，有過IM病史群體在類風溼關節炎（aHR＝4.52，95％CI 1.21－17.58）、系統性紅斑狼瘡（aHR＝13.58，CI 6.32－37.81）和全身血管炎（aHR＝5.93，CI 1.89－18.17）等系統性自體免疫的調整後危險比更高。此外，對於其中9種器官專一性自體免疫疾病，IM組調整後的風險比也明顯更高。結論：傳染性單核球增多症是罹患自身免疫性疾病的風險因子，暗示了EBV感染與自體免疫疾病發生扮演一定角色。

並列關鍵字

EBV病毒 ； 傳染性單核球增多症 ； 人類皰疹病毒第四型 ； 自體免疫疾病 ； 健保資料庫研究