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Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2013 Apr; Vol. 131 (4), pp. 1136-45. Date of Electronic Publication: 2013 Feb 04. - Publication Year :
- 2013
-
Abstract
- Background: Mutations in Janus kinase 3 (JAK3) are a cause of severe combined immunodeficiency, but hypomorphic JAK3 defects can result in a milder clinical phenotype, with residual development and function of autologous T cells. Maternal T-cell engraftment is a common finding in infants with severe combined immunodeficiency but is not typically observed in patients with residual T-cell development.<br />Objective: We sought to study in detail the molecular, cellular, and humoral immune phenotype and function of 3 patients with hypomorphic JAK3 mutations.<br />Methods: We analyzed the distribution and function of T and B lymphocytes in 3 patients and studied the in vitro and in vivo responses of maternal T lymphocytes in 1 patient with maternal T-cell engraftment and residual production of autologous T lymphocytes.<br />Results: B cells were present in normal numbers but with abnormal distribution of marginal zone-like and memory B cells. B-cell differentiation to plasmablasts in vitro in response to CD40 ligand and IL-21 was abolished. In 2 patients the T-cell repertoire was moderately restricted. Surprisingly, 1 patient showed coexistence of maternal and autologous T lymphocytes. By using an mAb recognizing the maternal noninherited HLA-A2 antigen, we found that autologous cells progressively accumulated in vivo but did not compete with maternal cells in vitro.<br />Conclusion: The study of 3 patients with hypomorphic JAK3 mutations suggests that terminal B-cell maturation/differentiation requires intact JAK3 function, even if partially functioning T lymphocytes are present. Maternal T-cell engraftment can occur in patients with JAK3 mutations despite the presence of autologous T cells.<br /> (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
- Subjects :
- B-Lymphocytes immunology
Base Sequence
Cell Differentiation immunology
Cell Proliferation
Child, Preschool
Female
Humans
Immunity, Maternally-Acquired
Infant
Janus Kinase 3 immunology
Male
Molecular Sequence Data
Pedigree
Primary Cell Culture
Severe Combined Immunodeficiency immunology
Severe Combined Immunodeficiency pathology
Signal Transduction
T-Lymphocytes immunology
B-Lymphocytes pathology
Gene Expression Regulation, Developmental immunology
Genetic Variation immunology
Janus Kinase 3 genetics
Severe Combined Immunodeficiency genetics
T-Lymphocytes pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 131
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23384681
- Full Text :
- https://doi.org/10.1016/j.jaci.2012.12.667