Details

Autor(en) / Beteiligte

• Miedema, Jelle R.
• de Jong, Lieke J.
• van Uden, Denise
• Bergen, Ingrid M.
• Kool, Mirjam
• Broos, Caroline E.
• Kahlmann, Vivienne
• Wijsenbeek, Marlies S.
• Hendriks, Rudi W.
• Corneth, Odilia B.J.

Titel

Circulating T cells in sarcoidosis have an aberrantly activated phenotype that correlates with disease outcome

Ist Teil von

• Journal of autoimmunity, 2023-10, p.103120-103120, Article 103120

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper (Th)17.1 signature, which correlates with non-resolving sarcoidosis. We hypothesize that the peripheral blood (PB) T cell phenotype may correlate with outcome. Objectives: To compare frequencies, phenotypes and function of circulating T cell populations in sarcoidosis patients with healthy controls (HCs) and correlate these parameters with outcome. We used multi-color flow cytometry to quantify activation marker expression on PB T cell subsets in treatment-naïve patients and HCs. The disease course was determined after 2-year follow-up. Cytokine production was measured after T cell stimulation in vitro. We observed significant differences between patients and HCs in several T cell populations, including CD8+ and CD4+ T cells, Th1/Th17 subsets, CD4+ T memory stem cells, regulatory T cells (Tregs) and γδ T cells. Decreased frequencies of CD4+ T cells and increased frequencies of Tregs and CD8+ γδ T cells correlated with worse outcome. Naïve CD4+ T cells displayed an activated phenotype with increased CD25 expression in patients with active chronic disease at 2-year follow-up. A distinctive Treg phenotype with increased expression of CD25, CTLA4, CD69, PD-1 and CD95 correlated with chronic sarcoidosis. Upon stimulation, both naïve and memory T cells displayed a different cytokine profile in sarcoidosis compared to HCs. Circulating T cell subpopulations of sarcoidosis patients display phenotypic abnormalities that correlate with disease outcome, supporting a critical role of aberrant T cell activation in sarcoidosis pathogenesis. •Disease course in sarcoidosis is highly variable and unpredictable.•The discovery of biomarkers to predict long term disease outcome can help clinical decision making.•Peripheral T cells differ between patients and controls in frequency and phenotype.•Aberrantly activated naïve and regulatory T cells correlate with worse long term outcome in sarcoidosis.•Stimulated naïve and memory T cells show an altered cytokine profile in sarcoidosis.