ArticleBlood2015
Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 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
- Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.Frontiers in immunology · 2021Pooled it
- The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses.The Journal of experimental medicine · 2018Trial
- Celiac disease and developmental delay as the first manifestations of tripeptidyl peptidase 2 deficiency.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Cellular senescence and cell therapy in cardiovascular diseases.Stem cell research & therapy · 2025Review
- T Cell Aging: An Important Target for Perioperative Immunomodulation.Clinical interventions in aging · 2025Review
- Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency.Viruses · 2024Article
- Haploinsufficiency in PTPN2 leads to early-onset systemic autoimmunity from Evans syndrome to lupus.The Journal of experimental medicine · 2024Article
- Deciphering the impact of TERT/telomerase on immunosenescence and T cell revitalization.Frontiers in immunology · 2024Review
- Emerging insights into atypical B cells in pediatric chronic infectious diseases and immune system disorders: T(o)-bet on control of B-cell immune activation.The Journal of allergy and clinical immunology · 2024Review
- Article
- Proteostasis in T cell aging.Seminars in immunology · 2023Review
- Gut microbiota facilitates adaptation of the plateau zokor (Frontiers in microbiology · 2023Article
- Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression.Nature communications · 2022Article
- CD21Frontiers in pediatrics · 2022Article
- Autoimmune lymphoproliferative syndrome identified through reverse phenotyping.Central-European journal of immunology · 2022Article
- Defining and targeting patterns of T cell dysfunction in inborn errors of immunity.Frontiers in immunology · 2022Review
- Hallmarks of T cell aging.Nature immunology · 2021Review
- Primary Immunodeficiency in Children With Autoimmune Cytopenias: Retrospective 154-Patient Cohort.Frontiers in immunology · 2021Article
- Identification and Splicing Characterization of NovelFrontiers in genetics · 2021Article
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoimmune cytopenia is a frequent manifestation of primary immunodeficiencies. Two siblings presented with Evans syndrome, viral infections, and progressive leukopenia. DNA available from one patient showed a homozygous frameshift mutation in tripeptidyl peptidase II (TPP2) abolishing protein expression. TPP2 is a serine exopeptidase involved in extralysosomal peptide degradation. Its deficiency in mice activates cell death programs and premature senescence. Similar to cells from naïve, uninfected TPP2-deficient mice, patient cells showed increased major histocompatibility complex I expression and most CD8(+) T-cells had a senescent CCR7-CD127(-)CD28(-)CD57(+) phenotype with poor proliferative responses and enhanced staurosporine-induced apoptosis. T-cells showed increased expression of the effector molecules perforin and interferon-γ with high expression of the transcription factor T-bet. Age-associated B-cells with a CD21(-) CD11c(+) phenotype expressing T-bet were increased in humans and mice, combined with antinuclear antibodies. Moreover, markers of senescence were also present in human and murine TPP2-deficient fibroblasts. Telomere lengths were normal in patient fibroblasts and granulocytes, and low normal in lymphocytes, which were compatible with activation of stress-induced rather than replicative senescence programs. TPP2 deficiency is the first primary immunodeficiency linking premature immunosenescence to severe autoimmunity. Determination of senescent lymphocytes should be part of the diagnostic evaluation of children with refractory multilineage cytopenias.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.