HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions.


Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
11 2022
Historique:
received: 21 04 2022
accepted: 01 07 2022
pubmed: 23 7 2022
medline: 30 11 2022
entrez: 22 7 2022
Statut: ppublish

Résumé

Cells of the innate and adaptive immune systems depend on proper actin dynamics to control cell behavior for effective immune responses. Dysregulated actin networks are known to play a pathogenic role in an increasing number of inborn errors of immunity. The WAVE regulatory complex (WRC) mediates branched actin polymerization, a process required for key cellular functions including migration, phagocytosis, vesicular transport, and immune synapse formation. Recent reports of pathogenic variants in NCKAP1L, a hematopoietically restricted gene encoding the HEM1 protein component of the WRC, defined a novel disease involving recurrent bacterial and viral infections, autoimmunity, and excessive inflammation (OMIM 141180). This review summarizes the diverse clinical presentations and immunological phenotypes observed in HEM1-deficient patients. In addition, we integrate the pathophysiological mechanisms described in current literature and highlight the outstanding questions for diagnosis and management of the HEM1 actin immunodysregulatory disorder.

Identifiants

pubmed: 35869404
doi: 10.1007/s10875-022-01327-0
pii: 10.1007/s10875-022-01327-0
pmc: PMC9700602
doi:

Substances chimiques

Actins 0
NCKAP1L protein, human 144351-15-5
Membrane Proteins 0

Types de publication

Journal Article Review Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1583-1592

Informations de copyright

© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Auteurs

Sarah Cook (S)

Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Vanderbilt University School of Medicine, Nashville, TN, USA.

Michael J Lenardo (MJ)

Vanderbilt University School of Medicine, Nashville, TN, USA. mlenardo@niaid.nih.gov.

Alexandra F Freeman (AF)

Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. freemaal@mail.nih.gov.

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Classifications MeSH