PO32 - Changes in T cell cytokine profiles at baseline associate with treatment response in the PREDMETH study
Vicky C.S. Bogaard (Netherlands)1; Willemijn L. Driesse (Netherlands)1; Marlies S. Wijsenbeek (Netherlands)1; Vivienne Kahlmann (Netherlands)1; Catharina C. Moor (Netherlands)1; Montse Janssen Bonás (Netherlands)2; Marcel Veltkamp (Netherlands)2; Rudi W. Hendriks (Netherlands)1; Jelle R. Miedema (Netherlands)1; Odilia B.J. Corneth (Netherlands)1;
1 - Centre of Excellence for Interstitial Lung Diseases and Sarcoidosis, Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; 2 - Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, The Netherlands;
Keywords: T cell cytokines; treatment response; PREDMETH;
Select the theme: Controversies in Sarcoidosis Treatment
Type: Original Papers
Presentation: Poster Presentation

Introduction: Treatment response in sarcoidosis is highly variable and biomarkers that predict lung function outcomes are lacking. Identifying early immunological markers of treatment response is critical for personalized treatment, enabling early stratification and tailored therapy in pulmonary sarcoidosis.

Objectives: To identify immunological features at baseline that associate with changes in Forced Vital Capacity (FVC) in patients enrolled in the PREDMETH study.

Materials and Methods: In the PREDMETH study (Kahlmann et. al., 2025), 137 treatment-naïve patients with pulmonary sarcoidosis included in 17 Dutch hospitals were randomized into a prednisone and a methotrexate treatment arm and followed longitudinally. Blood samples were collected across six standardized visits over two years. 51 sex and age-matched healthy controls (HCs) were sampled at a single time-point. Here, we assessed baseline peripheral blood T-cell phenotypes using high-dimensional (spectral) flow cytometry and quantified cytokine production upon stimulation in patients prior to treatment initiation. The primary outcome was change in FVC over 24 weeks. We defined responders as having a mean FVC increase >5% from baseline to 24 weeks, or non-responders as having a ≤5% increase in FVC.

Results: A total of n=99 patients and n=40 HCs were included in this analysis. Compared to HCs, patient-derived CD4 T cells displayed an altered cytokine profile with more cells producing IL-2, IL-17A and IL-10, but fewer producing IFNγ. Interestingly, naïve CD4 T cells already showed a more activated phenotype in patients, with increased proportions of IL-2, TNFα, IL-10 and GMCSF producing cells. Non-responders to prednisone, but not methotrexate, showed increased proportions of IL-2 and GMCSF-producing CD4 T cells, and increased proportions of IFNγ-producing naïve T cells at baseline compared to responders.

Conclusions: Our data show that the cytokine profile of CD4 T cells is altered in sarcoidosis patients, and that changes in this profile at baseline are associated with prednisone treatment response.