Increased proportions of circulating PD-1⁺ CD4⁺ memory T cells and PD-1⁺ regulatory T cells associate with good response to prednisone in pulmonary sarcoidosis

Background: 

The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4⁺ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. 

Methods:

We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. 

Results: 

Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4⁺ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1⁺CD4⁺ memory T cells and PD-1⁺ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25⁺ cells and increased fractions of PD-1⁺ cells within the CD4⁺ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. 

Conclusions: 

Increased proportions of circulating PD-1⁺CD4⁺ memory T cells and PD-1⁺ regulatory T cells and decreased proportions of CD25⁺CD4⁺ memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy. 

Trial registration: 

NL44805.078.13