Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis
Article first published online: 5 MAY 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 5, pages 1555–1563, May 2005
How to Cite
Farge, D., Henegar, C., Carmagnat, M., Daneshpouy, M., Marjanovic, Z., Rabian, C., Ilie, D., Douay, C., Mounier, N., Clave, E., Bengoufa, D., Cabane, J., Marolleau, J. P., Gluckman, E., Charron, D., Toubert, A. and for the Intensification et Autogreffe dans les Maladies Auto Immunes Résistantes (ISAMAIR) Study Group (2005), Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis & Rheumatism, 52: 1555–1563. doi: 10.1002/art.21036
- Issue published online: 5 MAY 2005
- Article first published online: 5 MAY 2005
- Manuscript Accepted: 15 FEB 2005
- Manuscript Received: 1 JUL 2004
- Délégation Régionale à la Recherche Clinique
- Assistance Publique Hôpitaux de Paris
- French Ministry of Health (Programme Hospitalier de Recherche Clinique). Grant Number: AOM 97-030
- Etablissement Français des Greffes
- Groupe Français de Recherche sur la Sclérodermie
- Association des Sclérodermiques de France
To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc).
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, α/β T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs).
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 (rs = −0.41, P = 0.001) and positively with CD19+ (rs = 0.35, P = 0.001) and CD20+ (rs = 0.34, P = 0.002) lymphocyte counts.
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.