論文No3995
History and Familial Aggregation of Immune-Mediated Diseases in Sarcoidosis
A Register-Based Case-Control-Family Study
Marios Rossides,Susanna Kullberg,Elizabeth V. Arkema
CHEST, Volume 166, Issue 5, p1082-1092, November 2024
要約
この研究は、サルコイドーシスと免疫介在性疾患（IMD）の関連性について、大規模なスウェーデンの国民登録データを基に調査したものです。
主な発見
サルコイドーシス患者は、一般集団と比較して、IMDを有する割合が高い：特に、結合組織疾患、細胞減少症、セリアック病との関連が強かった。
IMDは家族内で集積する傾向がある：特にセリアック病、細胞減少症、甲状腺炎、皮膚乾癬、炎症性腸疾患、免疫介在性関節炎、結合組織疾患との関連が強かった。
take home message
サルコイドーシスと免疫介在性疾患（IMD）には共通の原因がある可能性が高い：この研究結果は、サルコイドーシスとIMDが共通の遺伝的背景や免疫学的メカニズムを共有していることを示唆しています。
IMDの既往歴は、サルコイドーシスのリスク因子となる可能性がある：IMDを患ったことがある人は、サルコイドーシスを発症するリスクが高いと考えられます。
サルコイドーシスの家族歴がある人は、IMDの発症リスクも高い可能性がある：サルコイドーシス患者がいる家族では、他のIMDも発症しやすい傾向があると考えられます。
Background
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.
Research Question
Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis?
Study Design and Methods
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.
Results
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).
Interpretation
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.