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Blood. 2018 Jun 28;131(26):2967-2977. doi: 10.1182/blood-2017-10-809822. Epub 2018 May 4.

B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation.

Author information

1
Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA.
2
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
3
Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
4
Department of Pediatrics and.
5
Department of Immunology, Duke University Medical Center, Durham, NC.
6
Division of Allergy/Immunology/Blood & Marrow Transplantation, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA.
7
Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, CA.
8
University of Southern California Keck School of Medicine, Los Angeles, CA.
9
Bone Marrow Transplant Program, Memorial Sloan Kettering Cancer Center, New York, NY.
10
Division of Hematology, Primary Children's Hospital, University of Utah/Huntsman Cancer Institute, Salt Lake City, UT.
11
Department of Pediatrics, University of Montreal, CHU Sainte-Justine, Montreal, QC, Canada.
12
Section of Pediatric Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.
13
Pediatric Blood and Marrow Transplant Program, Hackensack University Medical Center, Hackensack, NJ.
14
Division of Blood and Marrow Transplantation & Allergy and Immunology, Children's National Medical Center, Washington, DC.
15
Centre of Chronic Immunodeficiency, Medical Center, and.
16
Faculty of Medicine, University of Freiburg, Freiburg, Germany.
17
Division of Pediatric Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA.
18
Mattel Children's Hospital, University of California, Los Angeles, Mattel Children's Hospital, Los Angeles, CA.
19
Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
20
Department of Microbiology, Infectious Disease and Immunology, University of Montreal, CHU Sainte-Justine, Montreal, QC, Canada; and.
21
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Abstract

Allogeneic hematopoietic stem cell transplant (HSCT) typically results in donor T-cell engraftment and function in patients with severe combined immunodeficiency (SCID), but humoral immunity, particularly when using donors other than matched siblings, is variable. B-cell function after HSCT for SCID depends on the genetic cause, the use of pre-HSCT conditioning, and whether donor B-cell chimerism is achieved. Patients with defects in IL2RG or JAK3 undergoing HSCT without conditioning often have poor B-cell function post-HSCT, perhaps as a result of impairment of IL-21 signaling in host-derived B cells. To investigate the effect of pre-HSCT conditioning on B-cell function, and the relationship of in vitro B-cell function to clinical humoral immune status, we analyzed 48 patients with IL2RG/JAK3 SCID who were older than 2 years after HSCT with donors other than matched siblings. T follicular helper cells (TFH) developed in these patients with kinetics similar to healthy young children; thus, poor B-cell function could not be attributed to a failure of TFH development. In vitro differentiation of B cells into plasmablasts and immunoglobulin secretion in response to IL-21 strongly correlated with the use of conditioning, donor B-cell engraftment, freedom from immunoglobulin replacement, and response to tetanus vaccine. Patients receiving immunoglobulin replacement who had normal serum immunoglobulin M showed poor response to IL-21 in vitro, similar to those with low serum IgM. In vitro response of B cells to IL-21 may predict clinically relevant humoral immune function in patients with IL2RG/JAK3 SCID after HSCT.

PMID:
29728406
PMCID:
PMC6024640
DOI:
10.1182/blood-2017-10-809822
[Indexed for MEDLINE]
Free PMC Article

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