ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1062

Lymphocyte Subset Abnormalities in Early Diffuse Cutaneous Systemic Sclerosis

David Fox1, Steven Lundy 2, Michael Whitfield 3, Veronica Berrocal 4, Phillip Campbell 5, Stephanie Rasmussen 5, Ray Ohara 6, Alexander Stinson 6, Evan Wiewiora 7, Cathie Spino 7, Erica Bush 8, Daniel Furst 9, Shiv Pillai 10 and Dinesh Khanna 11, 1Division of Rheumatology, Department of Internal Medicine, Autoimmunity Center of Excellence,University of Michigan, Ann Arbor, MI, 2SystImmune, Inc., Redmond, WA, 3Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hannover, NH, 4Department of Biostatistics, School of Publich Health, University of Michigan, Ann Arbor, MI, 5Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 6Washington University, St. Louis, MO, 7Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, 8Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 9University of California, Los Angeles, CA, 10Ragon Institude of MGH, MIT and Harvard, Charlestown, MA, 11Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, Autoimmunity Center of Excellence, University of Michigan, Ann Arbor

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: , ,

Session Information

Date: Monday, November 11, 2019

Session Title: Systemic Sclerosis & Related Disorders – Basic Science Poster

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. 

Disclosure: D. Fox, None; S. Lundy, None; M. Whitfield, BMS, 5, Boehringer Ingelheim, 5, Corbus Pharmaceuticals, 5, Third Rock Ventures, 5, Celdara Medical LLC, 2, 5, 7, 9; V. Berrocal, None; P. Campbell, None; S. Rasmussen, None; R. Ohara, None; A. Stinson, None; E. Wiewiora, None; C. Spino, Eicos, Inc., 5; E. Bush, None; D. Furst, Actelion, 2, 5, Actelion Pharmaceuticals, 2, 5, Amgen, 2, 5, BMS, 2, 5, CME, 5, 8, Corbus, 2, 5, Galapagos, 2, 5, Galapogos Novartis, 5, GlaxoSmithKline, 2, GSK, 2, 5, NIH, 2, Novartis, 2, 5, Pfizer, 2, 5, Roche/Genentech, 2, 5, Sanofi, 2, 5; S. Pillai, Abpro, 6; D. Khanna, Acceleron, 5, Actelion, 5, Bayer, 2, 5, Blade Therapeutics, 5, BMS, 2, 5, Boehringer Ingelheim, 5, Celegene, 5, ChemomAB, 5, Corubus, 5, CSL Behring, 5, Curzion, 5, Cytori, 5, Eicos, Inc, 4, Genentech, 5, GSK, 5, Horizon, 2, Mitsubishi Tanabe Pharma Development America, 5, Pfizer, 2, Sanofi-Aventis, 5, UCB, 5.

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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