Connective tissue disease-associated interstitial lung disease: immune profiling and correlation of immune cells with pulmonary function in SSc-ILD

Background Connective tissue diseases (CTDs) frequently involve the lungs, with CTD-associated interstitial lung disease (CTD-ILD) representing a leading cause of morbidity and mortality, yet the immunopathological mechanisms remain incompletely defined. This study characterized immune profiles in CTD-ILD and their association with pulmonary function impairment, focusing on systemic sclerosis-associated ILD (SSc-ILD).Methods This single-center retrospective study enrolled 217 CTD-ILD patients, 100 healthy controls, and 25 idiopathic pulmonary fibrosis (IPF) patients. Peripheral lymphocyte subsets, immunoglobulins, complements, and cytokines were assessed using flow cytometry and immunoturbidimetry. Lung function was evaluated by standard spirometry and gas transfer tests.Results Compared to healthy controls, lymphocyte counts were reduced in all ILD subtypes, lowest in polymyositis/dermatomyositis (PM/DM)-ILD. In SSc-ILD, T cell and helper T cell (Th) percentages were significantly elevated (76.2% and 49.39%, respectively). Complement C3 was lower in Sjögren’s syndrome (SS)-ILD (889.92 vs. 965.49 mg/L), and C4 was significantly lower in SSc-ILD (196.74 vs. 226.70 mg/L) versus controls. SSc-ILD patients with higher Th cell proportions exhibited worse pulmonary function, with expiratory reserve volume (ERV) falling 57.21%, maximal vital capacity (VC max) 18.81%, functional residual capacity (FRC) 19.64%, forced vital capacity (FVC)17.93%, and diffusing capacity for carbon monoxide (DLCO) 20.28%. Continuous correlation analysis further confirmed significant negative correlations between Th cell proportions and ERV, FRC, and PCO2.Conclusion Peripheral blood immune profiling revealed distinct abnormalities across CTD-ILD subtypes. Peripheral Th cell expansion is strongly associated with lung function decline in SSc-ILD, highlighting the potential of Th cells as biomarkers of disease progression in SSc-ILD.