4.7 Article

Lymphocyte subset abnormalities in early severe scleroderma favor a Th2 phenotype and are not altered by prior immunosuppressive therapy

Journal

RHEUMATOLOGY
Volume 61, Issue 10, Pages 4155-4162

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keac015

Keywords

scleroderma; lymphocyte subsets; clinical trial; stem cell transplantation; CYC

Categories

Funding

  1. National Institute of Allergy and Infectious Diseases (NIAID)
  2. NIH, Bethesda, MD, USA [AI05419, AI058607, HHSN 272201100025C]
  3. Alberta Heritage Foundation for Medical Research, Canada Research Chair Program
  4. Alberta Cancer Foundation
  5. Calgary, AB, Canada

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This study found significant abnormalities in lymphocyte subsets in patients with early, severe SSc, and prior immunosuppressive therapy did not affect the immunophenotype, suggesting that lymphocyte disturbances in scleroderma may be due to the disease itself.
Objectives. The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial compared hematopoietic stem cell transplant to CYC treatment in patients with early SSc with progressive skin and lung or kidney involvement. Here we describe lymphocyte phenotype abnormalities at study entry and the relation to prior DMARD therapy. Methods. Lymphocyte subsets (n = 26) measured by flow cytometry were compared in 123 heathy controls and 71 SCOT participants, including those given (n = 57) or not given (n = 14) DMARDs within 12 months of randomization. Results. Compared with healthy controls, individuals with SSc showed significant reductions in central memory CD8 T cells, activated total and CD4 T cells, gamma/delta T cells, memory B cells, myeloid and plasmacytoid dendritic cells and FOXP3(+)CD25(+) Treg cells and increases in naive CD4 T cells, effector memory CD4 T cells and effector CD8 T cells. A greater bias towards a IL-4(+) Th2fT cytotoxic 2 (Tc2) phenotype based on the Th2:Th1 CD4 ratio and Tc2:Tc1 CD8 T cells was also found. Notably, no difference in any lymphocyte subset was observed between those given or not given prior DMARDs. Conclusions. In patients with early, severe SSc, significant lymphocyte subset abnormalities were observed. Prior treatment with immunosuppressive therapy did not impact the immunophenotype, suggesting that lymphocyte disturbances in scleroderma appeared to be due to the disease itself.

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