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- Title
Longitudinal Evaluation of Immune Reconstitution and B-cell Function After Hematopoietic Cell Transplantation for Primary Immunodeficiency.
- Authors
Scarselli, Alessia; Cesare, Silvia; Capponi, Claudia; Cascioli, Simona; Romiti, Maria; Matteo, Gigliola; Simonetti, Alessandra; Palma, Paolo; Finocchi, Andrea; Lucarelli, Barbarella; Pinto, Rita; Rana, Ippolita; Palumbo, Giuseppe; Caniglia, Maurizio; Rossi, Paolo; Carsetti, Rita; Cancrini, Caterina; Aiuti, Alessandro
- Abstract
Purpose: 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. Conclusion: 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.
- Subjects
IMMUNODEFICIENCY; HEMATOPOIETIC stem cell transplantation; IMMUNE reconstitution inflammatory syndrome; B cells; SEVERITY of illness index; ANTIBODY formation; THERAPEUTICS; PHYSIOLOGY
- Publication
Journal of Clinical Immunology, 2015, Vol 35, Issue 4, p373
- ISSN
0271-9142
- Publication type
Article
- DOI
10.1007/s10875-015-0154-4