title: Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients.
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.
authors.affiliation: 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.|INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France. dominique.farge-bancel@aphp.fr.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France. dominique.farge-bancel@aphp.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.|Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.|Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Lucas C M
authors.initials: LC
authors.lastname: Arruda
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Brigant
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Douay
authors.affiliation: Département d'Hématologie, AP-HP, Hôpital Saint-Antoine, Paris, France.
authors.forename: Zora
authors.initials: Z
authors.lastname: Marjanovic
authors.affiliation: Service de Médecine Interne, Hôpital Pierre Zobda Quitman, Fort-de France, Martinique, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Deligny
authors.affiliation: Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
authors.forename: Guitta
authors.initials: G
authors.lastname: Maki
authors.affiliation: Eurocord-Monacord, AP-HP, Hôpital Saint-Louis, Paris, France.|Centre Scientifique de Monaco, Monaco, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: INSERM UMR-1160, Institut Universitaire d'Hématologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Moins-Teisserenc
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002452:Cell Count; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D045743:Scleroderma, Diffuse / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte
keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Systemic sclerosis; T cell repertoire