ArticleThe Journal of clinical investigation2019
Complement and inflammasome overactivation mediates paroxysmal nocturnal hemoglobinuria with autoinflammation.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- TNFSF10 drives hyperactive immune responses via NLRP3 inflammasome and endoplasmic reticulum stress in autoimmune and inflammatory diseases.Journal of advanced research · 2026Article
- Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression.International journal of molecular sciences · 2026Review
- Diacylglycerol kinase-ε is required for the formation of GPI-anchored CD14 and the LPS-induced proinflammatory responses of macrophages.Cell communication and signaling : CCS · 2026Article
- Preferential use of alkyl-acyl phosphatidylinositol for GPI biosynthesis and diagnostic potential of lipidomics for inherited GPI deficiencies.The Journal of biological chemistry · 2026Article
- Clonal expansion mechanisms in paroxysmal nocturnal hemoglobinuria.International journal of hematology · 2026Review
- Free GPIs and Comparison of GPI Structures Among Species.International journal of molecular sciences · 2025Review
- Pharmacological Therapies in Paroxysmal Nocturnal Haemoglobinuria: Focus on Complement Inhibition.Drugs · 2025Review
- Biosynthesis of GPI anchored proteins, its deficiencies and treatment.Journal of human genetics · 2025Review
- Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its role in glycosylphosphatidylinositol-anchored protein biogenesis.Nature communications · 2024Article
- [Glycosylphosphatidylinositol biosynthesis deficiency 15 caused byZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- Long noncoding RNA FAM157C contributes to clonal proliferation in paroxysmal nocturnal hemoglobinuria.Annals of hematology · 2023Article
- The inflammasomes: crosstalk between innate immunity and hematology.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Prevention of intrauterine fetal growth restriction by administrating C1q/TNF-related protein 6, a specific inhibitor of the alternative complement pathway.Journal of assisted reproduction and genetics · 2022Article
- Occurrence of a paroxysmal nocturnal hemoglobinuria clone in an essential thrombocythemia: a link betweenHaematologica · 2022Article
- Allogeneic stem cell transplantation-A curative treatment for paroxysmal nocturnal hemoglobinuria with PIGT mutation: A case report.World journal of clinical cases · 2022Article
- Sleep deprivation and NLRP3 inflammasome: Is there a causal relationship?Frontiers in neuroscience · 2022Review
- Rescue of Glycosylphosphatidylinositol-Anchored Protein Biosynthesis Using Synthetic Glycosylphosphatidylinositol Oligosaccharides.ACS chemical biology · 2021Article
- Functional Analysis of the GPI Transamidase Complex by Screening for Amino Acid Mutations in Each Subunit.Molecules (Basel, Switzerland) · 2021Article
- Classical complement and inflammasome activation converge in CD14highCD16- monocytes in HIV associated TB-immune reconstitution inflammatory syndrome.PLoS pathogens · 2021Article
- [Thrombocytopenia and thromboses in a young woman].Zeitschrift fur Rheumatologie · 2021Article
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Authors and funding
21 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored (GPI-anchored) proteins, resulting from a mutation in the X-linked gene PIGA. Here we report on a set of patients in whom PNH results instead from biallelic mutation of PIGT on chromosome 20. These PIGT-PNH patients have clinically typical PNH, but they have in addition prominent autoinflammatory features, including recurrent attacks of aseptic meningitis. In all these patients we find a germ-line point mutation in one PIGT allele, whereas the other PIGT allele is removed by somatic deletion of a 20q region comprising maternally imprinted genes implicated in myeloproliferative syndromes. Unlike in PIGA-PNH cells, GPI is synthesized in PIGT-PNH cells and, since its attachment to proteins is blocked, free GPI is expressed on the cell surface. From studies of patients' leukocytes and of PIGT-KO THP-1 cells we show that, through increased IL-1β secretion, activation of the lectin pathway of complement and generation of C5b-9 complexes, free GPI is the agent of autoinflammation. Eculizumab treatment abrogates not only intravascular hemolysis, but also autoinflammation. Thus, PIGT-PNH differs from PIGA-PNH both in the mechanism of clonal expansion and in clinical manifestations.
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