The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal

OBJECTIVES Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients. METHODS Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22) or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20). Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission. RESULTS The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed. CONCLUSIONS An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The circulating Treg/Th17 ratio could serve as an alternative marker for monitoring pulmonary sarcoidosis relapse after the end of corticosteroid treatment and for rapidly predicting the response to retreatment.