Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: A variety of abnormalities in lymphocyte surface markers and functional subsets have been described in patients with systemic sclerosis (SSc), but conflicting results abound, and these studies often examined patients with heterogeneous disease duration, clinical phenotype, exposure to immunosuppressive agents, and degree of organ involvement. We studied a clinically homogeneous group of 88 early diffuse cutaneous SSc patients who had not received immunosuppressive drugs and 25 matched healthy controls.
Methods: Methods: The SSc patients were participants in the ASSET study, a placebo-controlled blinded trial of abatacept in SSc. Lymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at the baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation in overnight cultures.
Results: Results: SSc patients had increased percentages of CD4+ T cells and B cells, but a lower percentage of CD8+ T cells compared to healthy control subjects. The CD4+CD28-negative population was expanded in SSc, in the CD4 subset. The number of CD40 ligand+ cells was expanded in the SSc patients (p=0.003), but another T cell activation marker CD69, did not show increased expression on SSc T cells. A notable expansion of CD319+ T cells was seen among the CD4+ cells, where they are barely detectable in healthy subjects (2.96% versus 0.8%, p< 0.001). These CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, and were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin. Frequencies of IL-4+ cells did not differ between SSc and controls, but expansion of IL-17 producing (2.38% versus 0.82%, p=0.007) and dual IL-4/IL-17 producing (1.16% versus 0.24%, p=0.023) cells was observed in SSc. Numbers of regulatory, and peripheral helper T cells were similar in SSc and control groups.
Conclusion: Conclusion: In this carefully selected group of early diffuse SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment of early diffuse SSc.
To cite this abstract in AMA style:Fox D, Lundy S, Whitfield M, Berrocal V, Campbell P, Rasmussen S, Ohara R, Stinson A, Wiewiora E, Spino C, Bush E, Furst D, Pillai S, Khanna D. Lymphocyte Subset Abnormalities in Early Diffuse Cutaneous Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/lymphocyte-subset-abnormalities-in-early-diffuse-cutaneous-systemic-sclerosis/. Accessed November 29, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lymphocyte-subset-abnormalities-in-early-diffuse-cutaneous-systemic-sclerosis/