Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden.
Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden.
Chest. 2024 Nov;166(5):1082-1092. doi: 10.1016/j.chest.2024.05.014. Epub 2024 Jun 8.
An autoimmune component in the cause of sarcoidosis has long been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause are limited.
Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis?
We conducted a case-control-family study (2001-2020). Patients with sarcoidosis (N = 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N = 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95% CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs.
Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7% vs 4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95% CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95% CI, 0.97-3.65), thyroiditis (OR, 1.72; 95% CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95% CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95% CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95% CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95% CI, 1.00-1.93).
This study showed that IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms.
自身免疫成分在结节病发病机制中的作用一直存在争议，但人群中与个体和家族中结节病相关的免疫介导疾病（IMD）聚集相关的基础数据有限，提示可能存在共同病因。
有 IMD 病史的患者发生结节病的风险是否更高，IMD 是否会在有结节病的家族中聚集？
我们进行了病例对照家族研究（2001-2020 年）。使用先前验证的定义（≥ 2 次国际疾病分类 [ICD] 编码的住院或门诊就诊），在瑞典国家患者登记处确定结节病患者（N=14146）。在诊断时，患者按出生年份、性别和居住地点与来自一般人群的最多 10 名对照参与者（N=118478）相匹配。通过患者登记处的 ICD 代码（1968-2020 年）确定患者、对照参与者及其一级亲属（多代登记处）的 IMD。采用条件逻辑回归估计患者和对照参与者以及一级亲属中与 IMD 相关的结节病的比值比（OR）和 95%置信区间（CI）。
与对照参与者相比（7.7%比 4.7%），结节病患者的 IMD 患病率更高，尤其是结缔组织疾病、细胞减少症和乳糜泻。IMD 存在家族聚集现象；与乳糜泻的关联最强（OR，2.09；95%CI，1.22-3.58），其次是细胞减少症（OR，1.88；95%CI，0.97-3.65）、甲状腺炎（OR，1.72；95%CI，1.14-2.60）、皮肤银屑病（OR，1.70；95%CI，1.34-2.15）、炎症性肠病（OR，1.53；95%CI，1.14-2.03）、免疫介导性关节炎（OR，1.49；95%CI，1.20-1.85）和结缔组织疾病（OR，1.39；95%CI，1.00-1.93）。
本研究表明 IMD 会增加结节病的发病风险，并且会在有结节病的家族中聚集，表明 IMD 和结节病之间存在共同的病因。我们的发现需要进一步评估共同的遗传机制。
