title: Longitudinal Evaluation of Immune Reconstitution and B-cell Function After Hematopoietic Cell Transplantation for Primary Immunodeficiency.
abstract: OBJECTIVE
  Hematopoietic cell transplantation (HCT) provides a curative therapy for severe forms of primary immunodeficiencies (PID). While the timing and extent of T-cell reconstitution following transplant for PID has been studied in depth, less is known about the kinetics of B-cell development and long-term restoration of humoral functions, which been often reported to be suboptimal after HCT.
  
  
  METHODS
  We studied longitudinally B-cell development and function in a cohort of 13 PID patients transplanted between 1997 and 2010, with a follow-up ranging from 0.7 to 15 years. Flow cytometric analysis of naïve and antigen-experienced B-cell subsets and in vitro functional responses to CpG were compared with data from healthy children and correlated with the degree of B-cell chimerism and in vivo antibody production.
  
  
  RESULTS
  We found that total memory B-cells count remained below normal levels for the first 2 years of follow up and progressively normalized. Switched memory B-cells (CD19+CD27+IgD-IgM-) were restored early and better than IgM memory B-cells (CD19+CD27+IgD+IgM+), which remained significantly reduced long-term. The recovery of memory B-cells correlated with good in vivo humoral function and normalization of CpG-response. A complete B-cell reconstitution was usually associated with donor B-cells chimerism and pre-transplant conditioning. Donor source and the underlying genetic defect represented also important variables.
  
  
  CONCLUSIONS
  Monitoring of phenotypic and functional changes on B-cells following HCT may prove clinically relevant to tailor patients' care. In particular the analysis of IgM memory and switched memory B-cells in addition to in vitro B-cells stimulation are recommended before Ig replacement therapy (IgRT) discontinuation.
authors: University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Alessia
authors: A
authors: Scarselli
authors: Silvia
authors: S
authors: Di Cesare
authors: Claudia
authors: C
authors: Capponi
authors: Simona
authors: S
authors: Cascioli
authors: Maria L
authors: ML
authors: Romiti
authors: Gigliola
authors: G
authors: Di Matteo
authors: Alessandra
authors: A
authors: Simonetti
authors: Paolo
authors: P
authors: Palma
authors: Andrea
authors: A
authors: Finocchi
authors: Barbarella
authors: B
authors: Lucarelli
authors: Rita M
authors: RM
authors: Pinto
authors: Ippolita
authors: I
authors: Rana
authors: Giuseppe
authors: G
authors: Palumbo
authors: Maurizio
authors: M
authors: Caniglia
authors: Paolo
authors: P
authors: Rossi
authors: Rita
authors: R
authors: Carsetti
authors: Caterina
authors: C
authors: Cancrini
authors: Alessandro
authors: A
authors: Aiuti
mesh_terms: D000293:Adolescent; D000917:Antibody Formation / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007109:Immunity; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D016130:Immunophenotyping; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007132:Immunoglobulin Isotypes