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

Author:

Shah Ankoor1,Storek Jan2,Woolson Rob3,Pinckney Ashley3,Keyes-Elstein Lynnette3,Wallace Paul K4,Sempowski Gregory D1,McSweeney Peter5,Mayes Maureen D6,Crofford Leslie7,Csuka M E8,Phillips Kristine7,Khanna Dinesh9,Simms Robert10,Ballen Karen11,LeClercq Sharon2,Clair William St1,Nixon Andrew B1,Nash Richard5,Wener Mark1213,Brasington Richard14,Silver Richard15,Griffith Linda M16,Furst Daniel E131718ORCID,Goldmuntz Ellen16,Sullivan Keith M1

Affiliation:

1. Department of Medicine, Duke University , Durham, NC, USA

2. Departments of Medicine and Oncology, University of Calgary , Calgary, AB, Canada

3. Rho Federal System , Durham, NC

4. Department of Oncology, Roswell Park Comprehensive Cancer Center , Buffalo, NY

5. Department of Hematology/Oncology, Colorado Blood Cancer Institute , Denver, CO

6. Department of Medicine, University of Texas , Houston, TX

7. Department of Medicine, Vanderbilt University Medical Center , Nashville, TN

8. Department of Medicine, Medical College of Wisconsin , Milwaukee, WI

9. Department of Medicine, University of Michigan , Ann Arbor, MI

10. Department of Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, NH

11. Department of Medicine, University of Virginia , Charlottesville, VA

12. Department of Oncology, Fred Hutchinson Cancer Research Center

13. Department of Medicine, University of Washington , Seattle, WA

14. Department of Medicine, Washington University , St. Louis, MO

15. Department of Medicine, Medical University of South Carolina , Charleston, SC

16. National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD

17. Department of Medicine, University of California , Los Angeles, CA, USA

18. University of Florence , Florence, Italy

Abstract

Abstract 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, γ/δ T cells, memory B cells, myeloid and plasmacytoid dendritic cells and FOXP3+CD25+ Treg cells and increases in naïve CD4 T cells, effector memory CD4 T cells and effector CD8 T cells. A greater bias towards a IL-4+ Th2/T 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. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT00114530.

Funder

National Institute of Allergy and Infectious Diseases

NIAID

NIH

Alberta Heritage Foundation for Medical Research, Canada Research Chair Program, Alberta Cancer Foundation, Calgary

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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