ArticleThe Journal of clinical investigation2011
Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.Frontiers in immunology · 2021Trial
- Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.Haematologica · 2015Trial
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Identifying genetic errors of immunity due to mosaicism.The Journal of experimental medicine · 2025Review
- Somatic mosaicism in genetic errors of immunity.The Journal of allergy and clinical immunology · 2025Review
- Somatic mutations in autoinflammatory and autoimmune disease.Nature reviews. Rheumatology · 2024Review
- Genetic Testing in Patients with Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.Journal of clinical immunology · 2024Article
- Study of the potential role of CASPASE-10 mutations in the development of autoimmune lymphoproliferative syndrome.Cell death & disease · 2024Article
- Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders.The Journal of allergy and clinical immunology · 2024Review
- Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.Molecular and cellular pediatrics · 2023Review
- Somatic mosaicism in inborn errors of immunity: Current knowledge, challenges, and future perspectives.Seminars in immunology · 2023Review
- Too much of a good thing: a review of primary immune regulatory disorders.Frontiers in immunology · 2023Review
- Nature and nurture: understanding phenotypic variation in inborn errors of immunity.Frontiers in cellular and infection microbiology · 2023Review
- Somatic mutations in rheumatological diseases: VEXAS syndrome and beyond.Rheumatology (Oxford, England) · 2022Review
- The contribution of rare copy number variants in FAS toward pathogenesis of autoimmune lymphoproliferative syndrome.Blood advances · 2022Article
- Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes.Genome medicine · 2022Article
- ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies.Annals of hematology · 2022Review
- Detection and evolutionary dynamics of somatic FAS variants in autoimmune lymphoproliferative syndrome: Diagnostic implications.Frontiers in immunology · 2022Article
- The genetic landscape of the FAS pathway deficiencies.Biomedical journal · 2021Review
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoimmune diseases develop in approximately 5% of humans. They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved in lymphocyte activation, survival, or death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects in self-tolerance checkpoints as a consequence of mutations in the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as FAS). However, some mutation carriers remain asymptomatic throughout life. We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele. Analysis of the patients' CD4(-)CD8(-) (double negative) T cells--accumulation of which is a hallmark of ALPS--revealed that in these cells, 3 patients had somatic mutations in their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10. This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases.
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