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01.05.2015 | Original Research

Longitudinal Evaluation of Immune Reconstitution and B-cell Function After Hematopoietic Cell Transplantation for Primary Immunodeficiency

verfasst von: Alessia Scarselli, Silvia Di Cesare, Claudia Capponi, Simona Cascioli, Maria L. Romiti, Gigliola Di Matteo, Alessandra Simonetti, Paolo Palma, Andrea Finocchi, Barbarella Lucarelli, Rita M. Pinto, Ippolita Rana, Giuseppe Palumbo, Maurizio Caniglia, Paolo Rossi, Rita Carsetti, Caterina Cancrini, Alessandro Aiuti

Erschienen in: Journal of Clinical Immunology | Ausgabe 4/2015

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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.

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Titel: Longitudinal Evaluation of Immune Reconstitution and B-cell Function After Hematopoietic Cell Transplantation for Primary Immunodeficiency
verfasst von: Alessia Scarselli
Silvia Di Cesare
Claudia Capponi
Simona Cascioli
Maria L. Romiti
Gigliola Di Matteo
Alessandra Simonetti
Paolo Palma
Andrea Finocchi
Barbarella Lucarelli
Rita M. Pinto
Ippolita Rana
Giuseppe Palumbo
Maurizio Caniglia
Paolo Rossi
Rita Carsetti
Caterina Cancrini
Alessandro Aiuti
Publikationsdatum: 01.05.2015
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 4/2015
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-015-0154-4

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