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

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

Author information

1
Unité de Médecine Interne, Maladies Autoimmunes et Pathologie Vasculaire, UF 04, Assistance Publique Hopitaux de Paris AP-HP, Hôpital Saint-Louis, Paris, France. dominique.farge-bancel@aphp.fr.
2
INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France. dominique.farge-bancel@aphp.fr.
3
Université Paris Diderot, Sorbonne Paris Cité, Paris, France. dominique.farge-bancel@aphp.fr.
4
INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.
5
Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.
6
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
7
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
8
Département d'Hématologie, AP-HP, Hôpital Saint-Antoine, Paris, France.
9
Service de Médecine Interne, Hôpital Pierre Zobda Quitman, Fort-de France, Martinique, France.
10
Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
11
Eurocord-Monacord, AP-HP, Hôpital Saint-Louis, Paris, France.
12
Centre Scientifique de Monaco, Monaco, France.

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

PMID:
28103947
PMCID:
PMC5244700
DOI:
10.1186/s13045-016-0388-5
[Indexed for MEDLINE]
Free PMC Article

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