发现自身免疫性疾病会影响大约十分之一的人

诸平

据英国牛津大学（University of Oxford）2023年5月5日提供的消息，新研究发现自身免疫性疾病会影响大约十分之一的人（Autoimmune disorders found to affect around one in ten people）。

一项针对2200万人的新的基于人群的研究表明，自身免疫性疾病现在影响大约十分之一的人。发表在《柳叶刀》（The Lancet）杂志网站上的这项工作，还强调了几种自身免疫性疾病的重要社会经济、季节和区域差异，并为这些疾病背后的可能原因提供了新线索。 详见Nathalie Conrad, Shivani Misra, Jan Y Verbakel, Prof Geert Verbeke, Prof Geert Molenberghs, Peter N Taylor, Prof Justin Mason, Prof Naveed Sattar, Prof John J V McMurray, Prof Iain B McInnes, Prof Kamlesh Khunti, Prof Geraldine Cambridge. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. The Lancet, Published:May 05, 2023. DOI: 10.1016/S0140-6736(23)00457-9. https://doi.org/10.1016/S0140-6736(23)00457-9

当免疫系统抵御感染的正常作用受到干扰，导致其错误地攻击体内正常的健康细胞时，就会发生自身免疫性疾病。此类疾病的例子包括类风湿性关节炎（rheumatoid arthritis）、1型糖尿病（type 1 diabetes）和多发性硬化症（multiple sclerosis），已知的自身免疫性疾病（autoimmune diseases）有80多种。

据报道，一些自身免疫性疾病，如1型糖尿病，在过去几十年中有所增加，这引发了一个问题，即自身免疫性疾病的总体发病率是否正在上升，这可能是由共同的环境因素或行为改变驱动的。自身免疫性疾病的确切原因，特别是在遗传易感性或环境因素的相对贡献方面，在很大程度上也仍然是个谜，需要进行大量研究。由于个体自身免疫性疾病很少见，而且自身免疫性疾病种类繁多，因此很难进行足够大的研究并建立可靠的估计来回答这些问题。

来自比利时鲁汶大学（KU Leuven）、英国伦敦大学学院（University College London）、英国格拉斯哥大学（University of Glasgow）、伦敦帝国理工学院（Imperial College London）、卡迪夫大学（Cardiff University）、莱斯特大学（University of Leicester）以及牛津大学（University of Oxford）的流行病学（epidemiology）、生物统计学（biostatistics）、风湿病学（rheumatology）、内分泌学（endocrinology）和免疫学（immunology）专家联盟聚集在一起回答其中一些问题。

该研究使用来自英国的2200万人的一个非常大的匿名电子健康记录数据集来调查19种最常见的自身免疫性疾病。作者检查了自身免疫性疾病的病例是否随着时间的推移而增加，哪些人受这些疾病的影响最大，以及不同的自身免疫性疾病如何相互共存。

他们发现，将所研究的这19种自身免疫性疾病加在一起，影响了大约 10% 的人口 -13%的女性和7%的男性。这高于之前的估计，之前的估计范围为3%~9%，并且通常依赖于较小的样本量并且包括较少的自身免疫性疾病。

他们还发现了几种自身免疫性疾病之间存在社会经济、季节性和区域差异的证据。他们认为，这种变异不太可能仅归因于遗传差异，并且可能表明存在潜在可改变的风险因素，例如吸烟、肥胖或压力，这些因素会导致某些自身免疫性疾病的发展。

最后，他们的研究还证实，在某些情况下，与没有自身免疫性疾病的人相比，患有一种自身免疫性疾病的人更有可能患上第二种疾病。这些发现揭示了新的模式，这些模式可能会为进一步研究不同自身免疫性疾病表现背后可能的常见原因的设计提供信息。

该论文的第一作者、牛津大学纳菲尔德妇女与生殖健康系深度医学（Deep Medicine, Nuffield Department of Women’s & Reproductive Health, University of Oxford）的娜塔莉·康拉德（Nathalie Conrad）博士评论道：“我们观察到，一些自身免疫性疾病往往与其他疾病共同发生，这比人们偶然或单独增加监测所预期的更频繁。这可能意味着某些自身免疫性疾病具有共同的风险因素，例如遗传易感性或环境诱因，这在风湿性疾病和内分泌疾病中尤为明显。但这种现象并没有在所有自身免疫性疾病中普遍存在——例如，多发性硬化症与其他自身免疫性疾病的共病率很低，这表明其具有独特的病理生理学（pathophysiology）。

该论文的资深作者、伦敦大学学院的杰拉尔丁·坎布里奇（Geraldine Cambridge）教授说：“我们的研究强调了自身免疫性疾病给个人和更广泛人群带来的巨大负担。理清这一庞大而多样的条件中的共性和差异是一项复杂的任务。因此，迫切需要加强旨在了解这些情况的根本原因的研究工作，这将支持制定有针对性的干预措施，以减少环境和社会风险因素的影响。”
本研究得到了佛兰德斯研究基金（Research Foundation Flanders）的资助。

上述介绍，仅供参考。欲了解更多信息，敬请注意浏览原文或者相关报道。

Summary

Background

A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases.

Methods

In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex.

Findings

Among the 22009375 individuals included in the study, 978872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54.0 years [SD 21.4]). 625879 (63.9%) of these diagnosed individuals were female and 352993 (36.1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017–19 vs 2000–02 1.04 [95% CI 1.00–1.09]). The largest increases were seen in coeliac disease (2.19 [2.05–2.35]), Sjogren's syndrome (2.09 [1.84–2.37]), and Graves' disease (2.07 [1.92–2.22]); pernicious anaemia (0.79 [0.72–0.86]) and Hashimoto's thyroiditis (0.81 [0.75–0.86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10.2% of the population over the study period (1912200 [13.1%] women and 668264 [7.4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1.72 [1.64–1.81]), rheumatoid arthritis (1.52 [1.45–1.59]), Graves' disease (1.36 [1.30–1.43]), and systemic lupus erythematosus (1.35 [1.25–1.46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26.5 [95% CI 17.3–40.7]), coeliac disease (28.4 [25.2–32.0]), and thyroid disease (Hashimoto's thyroiditis 13.3 [11.8–14.9] and Graves' disease 6.7 [5.1–8.5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases.

Interpretation

Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases.