Increased circulating PD-1+CD4+ memory T cell and PD-1+ regulatory T cell proportions associate with prednisone efficacy in sarcoidosis

The efficacy of corticosteroid treatment in patients with pulmonary sarcoidosis is highly variable. CD4⁺ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease progression. Therefore, we hypothesized that PB T cell phenotypes in patients with sarcoidosis correlate with treatment response and aim to correlate baseline T cell phenotypes with pulmonary function response in patients receiving prednisone. Multi-color flow cytometry was used to quantify activation marker expression on PB T cell populations in 22 treatment-naive patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. Patients with sarcoidosis showed a forced vital capacity (FVC) increase of ~14.0% (IQR 5.8-19.5; p<0.0001) between baseline and 3 months. Results showed that good responders (defined as FVC increase ≥10%) had significantly increased baseline proportions of PD-1⁺CD4⁺ Tm cells and PD-1⁺ Tregs at 3 months compared to poor responders and HCs. Moreover, decreased fractions of CD25⁺ cells and increased fractions of PD-1⁺ cells within the CD4⁺ Tm cell population correlated with an FVC increase of ≥10% at 12 months. During treatment, the aberrantly activated phenotype of CD4⁺ Tm and Treg cells reversed. In conclusion, increased proportions of circulating PD-1⁺CD4⁺ Tm cells and PD-1⁺ Tregs associate with a good initial FVC response to prednisone in pulmonary sarcoidosis. Long-term FVC improvement is correlated with higher CD4⁺PD-1⁺ and lower CD4⁺CD25⁺ Tm cell proportions. These findings represent promising new biomarkers of prednisone efficacy.