Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

J Hematol Oncol. 2017 Jan 19;10(1):21. doi: 10.1186/s13045-016-0388-5.

Abstract

The determinants of clinical responses after autologous hematopoietic stem cell transplantation (aHSCT) in systemic sclerosis (SSc) are still unraveled. We analyzed long-term immune reconstitution (IR) and T cell receptor (TCR) repertoire diversity in 10 SSc patients, with at least 6 years simultaneous clinical and immunological follow-up after aHSCT. Patients were retrospectively classified as long-term responders (A, n = 5) or non-responders (B, n = 5), using modified Rodnan's skin score (mRSS) and forced vital capacity (FVC%). All patients had similar severe SSc before aHSCT. Number of reinjected CD34+ cells was higher in group B versus A (P = 0.02). Long-term mRSS fall >25% was more pronounced in group A (P = 0.004), the only to improve long-term FVC% >10% (P = 0.026). There was an overall trend toward increased of T cell reconstitution in group B versus A. B cells had a positive linear regression slope in group A (LRS = 11.1) and negative in group B (LRS = -11.6). TCR repertoire was disturbed before aHSCT and the percentage of polyclonal families significantly increased at long-term (P = 0.046), with no difference between groups. Despite improved skin score after aHSCT in all SSc patients, pretransplant B cell clonal expansion and faster post-transplant T cell IR in long-term non-responder/relapsing patients call for new therapeutic protocols guided by IR analysis to improve their outcome.

Keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Systemic sclerosis; T cell repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Cell Count
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Scleroderma, Diffuse / immunology
  • Scleroderma, Diffuse / pathology
  • Scleroderma, Diffuse / therapy*
  • Severity of Illness Index
  • Skin / immunology
  • Skin / pathology
  • T-Lymphocyte Subsets / immunology*
  • Transplantation, Autologous
  • Young Adult

Substances

  • Antigens, Differentiation, T-Lymphocyte