title: Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis.
abstract: OBJECTIVE
  To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc).
  
  
  METHODS
  Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, alpha/beta T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs).
  
  
  RESULTS
  Patients had similar characteristics at study entry, except for a lower modified Rodnan skin thickness score (P = 0.03) and a lower Health Assessment Questionnaire score (P = 0.05) in group A than in group B. The number of reinjected cells and the time to hematopoietic reconstitution were similar in both groups. The absolute numbers of CD19+ and CD20+ B cells were lower in group A than in normal controls (P < 0.05) and within the normal range in group B. Absolute numbers of T and natural killer lymphocytes were normal before HSCT. Numbers of CD3+ cells remained low thereafter. Numbers of CD8+ cells were back to normal 3 months after HSCT in both groups. B cell counts were low until 6 months after HSCT in group A and stayed in the normal range in group B. The CD3+ defect was sustained in group A, with an opposite trend and a faster CD4+ reconstitution profile in group B. The T cell repertoire was skewed before and until 1 year after HSCT, with shared expansions before and after transplant in a given individual. TREC values correlated negatively with C-reactive protein levels (r(s) = -0.41, P = 0.001) and positively with CD19+ (r(s) = 0.35, P = 0.001) and CD20+ (r(s) = 0.34, P = 0.002) lymphocyte counts.
  
  
  CONCLUSIONS
  B and T lymphocyte populations remained disturbed for at least 1 year after HSCT in SSc patients, which may reflect the persistence of an underlying disease mechanism.
authors.affiliation: Hôpital Saint-Louis, Paris, France. farge-bancel@sls.ap-hop-paris.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge
authors.forename: Corneliu
authors.initials: C
authors.lastname: Henegar
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.forename: Marjan
authors.initials: M
authors.lastname: Daneshpouy
authors.forename: Zora
authors.initials: Z
authors.lastname: Marjanovic
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Doina
authors.initials: D
authors.lastname: Ilie
authors.forename: Corinne
authors.initials: C
authors.lastname: Douay
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Djaouida
authors.initials: D
authors.lastname: Bengoufa
authors.forename: Jean
authors.initials: J
authors.lastname: Cabane
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000601:surgery*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology