Title |
Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome
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Published in |
The Journal of Experimental Medicine, February 2013
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DOI | 10.1084/jem.20111229 |
Pubmed ID | |
Authors |
Daniel Kotlarz, Natalia Ziętara, Gulbu Uzel, Thomas Weidemann, Christian J. Braun, Jana Diestelhorst, Peter M. Krawitz, Peter N. Robinson, Jochen Hecht, Jacek Puchałka, E. Michael Gertz, Alejandro A. Schäffer, Monica G. Lawrence, Lela Kardava, Dietmar Pfeifer, Ulrich Baumann, Eva-Doreen Pfister, Eric P. Hanson, Axel Schambach, Roland Jacobs, Hans Kreipe, Susan Moir, Joshua D. Milner, Petra Schwille, Stefan Mundlos, Christoph Klein |
Abstract |
Primary immunodeficiencies (PIDs) represent exquisite models for studying mechanisms of human host defense. In this study, we report on two unrelated kindreds, with two patients each, who had cryptosporidial infections associated with chronic cholangitis and liver disease. Using exome and candidate gene sequencing, we identified two distinct homozygous loss-of-function mutations in the interleukin-21 receptor gene (IL21R; c.G602T, p.Arg201Leu and c.240_245delCTGCCA, p.C81_H82del). The IL-21R(Arg201Leu) mutation causes aberrant trafficking of the IL-21R to the plasma membrane, abrogates IL-21 ligand binding, and leads to defective phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5. We observed impaired IL-21-induced proliferation and immunoglobulin class-switching in B cells, cytokine production in T cells, and NK cell cytotoxicity. Our study indicates that human IL-21R deficiency causes an immunodeficiency and highlights the need for early diagnosis and allogeneic hematopoietic stem cell transplantation in affected children. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Hungary | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Denmark | 1 | <1% |
Germany | 1 | <1% |
Taiwan | 1 | <1% |
Unknown | 170 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 42 | 24% |
Student > Ph. D. Student | 36 | 21% |
Student > Bachelor | 16 | 9% |
Student > Doctoral Student | 11 | 6% |
Other | 11 | 6% |
Other | 37 | 21% |
Unknown | 21 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 46 | 26% |
Immunology and Microbiology | 34 | 20% |
Medicine and Dentistry | 30 | 17% |
Biochemistry, Genetics and Molecular Biology | 21 | 12% |
Nursing and Health Professions | 3 | 2% |
Other | 10 | 6% |
Unknown | 30 | 17% |