Paroxysmal nocturnal hemoglobinuria
Open accessAbstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations. GPI anchor protein deficiency is almost always due to somatic mutations in phosphatidylinositol glycan class A (PIGA), a gene involved in the first step of GPI anchor biosynthesis; however, alternative mutations that cause PNH have recently been discovered. In addition, hypomorphic germ-line PIGA mutations that do not cause PNH have been shown to be responsible for a condition known as multiple congenital anomalies-hypotonia-seizures syndrome 2. Eculizumab, a first-in-class monoclonal antibody that inhibits terminal complement, is the treatment of choice for patients with severe manifestations of PNH. Bone marrow transplantation remains the only cure for PNH but should be reserved for patients with suboptimal response to eculizumab.
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The PIGA gene is required for the synthesis of glycophosphotidylinositol (GPI) and its loss results in down-regulation of several cell surface proteins that are GPI anchored.
“The PIGA gene is required for the synthesis of glycophosphotidylinositol (GPI) and its loss results in down-regulation of several cell surface proteins that are GPI anchored 60.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [60]
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Clonal hematopoiesis in human aging and disease
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“The PIGA gene is required for the synthesis of glycophosphatidylinositol (GPI), and its loss results in down-regulation of several cell surface proteins that are GPI anchored (61).”
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- Authors
- Brodsky, R. A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Brodsky, Robert A.
- ORCID
- Brodsky, Robert A.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2014-10-30
- Volume
- 124
- Issue
- 18
- Pages
- 2804-2811
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4215311
- OpenAlex
- W1978700432
- Cited by
- 648
- References
- 90
- Citations by year
- 2026: 60 · 2025: 64 · 2024: 64 · 2023: 50 · 2022: 68 · 2021: 66 · 2020: 60 · 2019: 52 · 2018: 39 · 2017: 38 · 2016: 29 · 2015: 41 · 2014: 8 · 2013: 8 · 2012: 1
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Maryland Stem Cell Research Fund
- National Institutes of Health
- National Cancer Institute (P01-CA70970, P01CA070970)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- paroxysmal nocturnal hemoglobinuria, bone marrow failure, hemolytic anemia, thrombosis, CD55, CD59, complement activation, PIG-A mutation, glycosylphosphatidylinositol anchor biosynthesis, eculizumab, complement inhibition, bone marrow transplantation
- MeSH terms
- Hemoglobinuria, Paroxysmal, Humans, Monitoring, Physiologic, Mutation, Bone Marrow Transplantation, Glycosylphosphatidylinositols
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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