Thymic characteristics in patients with autoimmune diseases: a multicentre radiological observational study.

Background: Autoimmune diseases comprise a spectrum of illnesses stemming from a common etiology: the loss of self-tolerance. The organ crucial for the establishment and maintenance of central and peripheral tolerance, namely the thymus, has rarely been explored across these diseases. Methods: In a multicentre radiological case-control study, we characterized the thymus in 16 prevalent autoimmune diseases using chest computed tomography (CT) images from patients and age- and sex-1:1 matched healthy controls. Participants underwent a routine CT examination, and baseline information on demographic, clinical, and potential risk factors was gathered at the time of enrollment. A semi-automatic algorithm was developed and employed for the analysis of thymic radiological characteristics, encompassing structural features and density. Thymic fatty replacement was evaluated using a four-point visual scoring scale (0-3). This study is registered with the Chinese Clinical Trial Registry (ChiCTR2300078417). Findings: After matching, 2441 participants in each group were included in case-control study. As individuals age, the thymus undergoes involution, leading to marked changes in thymic features over time, yet the degree of thymic feature alterations varies among groups. Compared to healthy controls, multiple characteristics of the thymus were distinct in the autoimmune disease patients, featuring higher trapezoidal proportions (68.21% vs 46.29%; p < 0.0001), larger bilobed size, and reduced density (-9.50; 95% CI, -10.95 to -8.04; p < 0.0001). In addition, the autoimmune disease patients displayed a greater proportion of fatty replacement (score 0, score 1, and score 2, 94.23% vs 87.83%, p < 0.0001). This consistent trend of thymic characteristic alternations, was observed across the 16 diseases (albeit varying in degree) and in newly diagnosed as early-stage patients. Notably, the subgroup for female patients of childbearing age (≤49 years) exhibited an especially prominent difference in thymic density (-16.23; 95% CI, -19.19 to -13.26; p < 0.0001 in all comparisons) and in the proportion of fatty replacement (85.37% vs 71.68%; p < 0.0001). Interpretation: Radiological assessments reveal a consistent pattern of exacerbated age-dependent thymic involution across 16 autoimmune diseases, suggesting a common underlying mechanism in the development of these diseases. This mechanism may involve the compromise of self-tolerance due to thymic involution. Funding: The National Key R&D Program of China, the National Science Foundation of China, and the Tianjin Key Medical Discipline (Specialty) Construction Project.