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CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis
- Source :
- Blood
- Publication Year :
- 2019
- Publisher :
- American Society of Hematology, 2019.
-
Abstract
- Dysregulated immune responses are essential underlying causes of a plethora of pathologies including cancer, autoimmunity, and immunodeficiency. We here investigated 4 patients from unrelated families presenting with immunodeficiency, autoimmunity, and malignancy. We identified 4 distinct homozygous mutations in TNFRSF9 encoding the tumor necrosis factor receptor superfamily member CD137/4-1BB, leading to reduced, or loss of, protein expression. Lymphocytic responses crucial for immune surveillance, including activation, proliferation, and differentiation, were impaired. Genetic reconstitution of CD137 reversed these defects. CD137 deficiency is a novel inborn error of human immunity characterized by lymphocytic defects with early-onset Epstein-Barr virus (EBV)-associated lymphoma. Our findings elucidate a functional role and relevance of CD137 in human immune homeostasis and antitumor responses.
- Subjects :
- Male
Lymphoma
Immunobiology and Immunotherapy
Immunology
medicine.disease_cause
Biochemistry
Virus
Autoimmune Diseases
Autoimmunity
Tumor Necrosis Factor Receptor Superfamily, Member 9
03 medical and health sciences
0302 clinical medicine
Immune system
Immunity
Humans
Medicine
Genetic Predisposition to Disease
Immunodeficiency
030304 developmental biology
0303 health sciences
Mutation
business.industry
CD137
Immunologic Deficiency Syndromes
Cell Biology
Hematology
Immune dysregulation
medicine.disease
Pedigree
3. Good health
Female
business
030215 immunology
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 134
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....fa25860946903a86c425767a7871af65