ArticleThe Journal of clinical investigation2018
Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Autosomal dominant gain-of-function mutations in LCP1 cause a syndromic neutropenia and immunodeficiency.Genes & diseases · 2027Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Review
- Inborn Errors of Immunity Presenting with Early-Onset Severe Atopy.Medicina (Kaunas, Lithuania) · 2025Review
- INTEGRIN FUNCTION IN LEUKOCYTE-MEDIATED INFLAMMATION-ACTINOPATHIES IN IMMUNE DISEASES.Transactions of the American Clinical and Climatological Association · 2025Review
- A first-in-class Wiskott-Aldrich syndrome protein activator with antitumor activity in hematologic cancers.Haematologica · 2024Article
- Association of neutrophil defects with oral ulcers but undetermined role of neutrophils in recurrent aphthous stomatitis.Heliyon · 2024Review
- Small GTPase Cdc42, WASP, and scaffold proteins for higher-order assembly of the F-BAR domain protein.Science advances · 2023Article
- Not too little, not too much: the impact of mutation types in Wiskott-Aldrich syndrome and RAC2 patients.Clinical and experimental immunology · 2023Review
- A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome.Blood advances · 2022Article
- Review
- WASP integrates substrate topology and cell polarity to guide neutrophil migration.The Journal of cell biology · 2022Article
- RHO GTPases: from new partners to complex immune syndromes.Nature reviews. Immunology · 2021Review
- Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells.JCI insight · 2021Article
- Clinical Features, Cancer Biology, Transplant Approach and Other Integrated Management Strategies for Wiskott-Aldrich Syndrome.Journal of multidisciplinary healthcare · 2021Review
- When Actin is Not Actin' Like It Should: A New Category of Distinct Primary Immunodeficiency Disorders.Journal of innate immunity · 2021Review
- Molecular Mechanisms of Leukocyte Migration and Its Potential Targeting-Lessons Learned From MKL1/SRF-Related Primary Immunodeficiency Diseases.Frontiers in immunology · 2021Review
- Zebrafish Cancer Predisposition Models.Frontiers in cell and developmental biology · 2021Review
- Journey to the Center of the Cell: Cytoplasmic and Nuclear Actin in Immune Cell Functions.Frontiers in cell and developmental biology · 2021Review
- Molecular Tuning of Actin Dynamics in Leukocyte Migration as Revealed by Immune-Related Actinopathies.Frontiers in immunology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. XLN patients had reduced myelopoiesis and extremely low blood neutrophil number. However, their neutrophils had a hyperactive phenotype and were present in normal numbers in XLN patient saliva. Murine XLN neutrophils were hyperactivated, with increased actin dynamics and migration into tissues. We provide molecular evidence that the hyperactivity of XLN neutrophils is caused by WASp in a constitutively open conformation due to contingent phosphorylation of the critical tyrosine-293 and plasma membrane localization. This renders WASp activity less dependent on regulation by PI3K. Our data show that the amplitude of WASp activity inside a cell could be enhanced by cell-surface receptor signaling even in the context in which WASp is already in an active conformation. Moreover, these data categorize XLN as an atypical congenital neutropenia in which constitutive activation of WASp in tissue neutrophils compensates for reduced myelopoiesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.