Frequency of circulating topoisomerase-I-specific CD4 T cells predicts presence and progression of interstitial lung disease in scleroderma. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Fava, Andrea; Cimbro, Raffaello; Wigley, Fredrick M.; Liu, Qing-Rong; Rosen, Antony; Boin, Francesco
• Is Part Of: Arthritis research & therapy. Volume 18:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: Systemic sclerosis -- Interstitial lung disease -- T lymphocytes -- Th17 -- Autoantigen; Arthritis -- Periodicals; Arthritis -- Treatment -- Periodicals; 616.722005
• DOI: 10.1186/s13075-016-0993-2
• Languages: English
• ISSNs: 1478-6362

Abstract

Abstract Background Scleroderma is an antigen-driven T cell-mediated autoimmune disease. Presence of anti-topoisomerase-I antibodies is associated with pulmonary fibrosis and predicts increased mortality. Characterization of autoreactive T lymphocytes may shed light on disease pathogenesis and serve as a biomarker for disease activity. Here, we aimed to quantify and functionally characterize circulating topoisomerase I (topo-I)-specific CD4+ T cells and to define their association with presence and progression of interstitial lung disease (ILD) in patients with scleroderma. Methods Using flow cytometry, circulating topo-I-reactive CD4+ T cells were identified by the expression of specific activation markers (CD154 and CD69) upon stimulation with purified topo-I and quantified in 27 SSc patients and 4 healthy donors (HD). Polarization of autoreactive T cells (Th1, Th2, Th17, Th1–17) was defined using surface expression of specific chemokine receptors. Presence and progression of ILD were determined using high-resolution chest CT and pulmonary function tests. Results Topo-I-reactive CD4+ T cells were found in all topo-I-positive patients compared to one topo-I-negative subject and no HD. Topo-I-specific CD4+ T cells exhibited a distinct Th17 polarized phenotype. Autoreactive T cells were significantly increased in subjects with evidence of ILD and were quantitatively associated with the decline of lung volumes. Conclusions Topo-I-specific T cells can be reliably quantified in the peripheral blood of patients with scleroderma, exhibit a pro-inflammatory Th17 phenotype, and predict progression of ILD.