NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation

Castro, Carla Noemi and Rosenzwajg, Michelle and Carapito, Raphael and Shahrooei, Mohammad and Konantz, Martina and Khan, Amjad and Miao, Zhichao and Groß, Miriam and Tranchant, Thibaud and Radosavljevic, Mirjana and Paul, Nicodème and Stemmelen, Tristan and Pitoiset, Fabien and Hirschler, Aurélie and Nespola, Benoit and Molitor, Anne and Rolli, Véronique and Pichot, Angélique and Faletti, Laura Eva and Rinaldi, Bruno and Friant, Sylvie and Mednikov, Mark and Karauzum, Hatice and Aman, M. Javad and Carapito, Christine and Lengerke, Claudia and Ziaee, Vahid and Eyaid, Wafaa and Ehl, Stephan and Alroqi, Fayhan and Parvaneh, Nima and Bahram, Seiamak. (2020) NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation. Journal of Experimental Medicine, 217 (12). e20192275.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/80783/

Downloads: Statistics Overview


The Nck-associated protein 1-like (NCKAP1L) gene, alternatively called hematopoietic protein 1 (HEM-1), encodes a hematopoietic lineage-specific regulator of the actin cytoskeleton. Nckap1l-deficient mice have anomalies in lymphocyte development, phagocytosis, and neutrophil migration. Here we report, for the first time, NCKAP1L deficiency cases in humans. In two unrelated patients of Middle Eastern origin, recessive mutations in NCKAP1L abolishing protein expression led to immunodeficiency, lymphoproliferation, and hyperinflammation with features of hemophagocytic lymphohistiocytosis. Immunophenotyping showed an inverted CD4/CD8 ratio with a major shift of both CD4+ and CD8+ cells toward memory compartments, in line with combined RNA-seq/proteomics analyses revealing a T cell exhaustion signature. Consistent with the core function of NCKAP1L in the reorganization of the actin cytoskeleton, patients' T cells displayed impaired early activation, immune synapse morphology, and leading edge formation. Moreover, knockdown of nckap1l in zebrafish led to defects in neutrophil migration. Hence, NCKAP1L mutations lead to broad immune dysregulation in humans, which could be classified within actinopathies.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin
UniBasel Contributors:Konantz, Martina
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:09 Jun 2021 13:36
Deposited On:09 Jun 2021 13:36

Repository Staff Only: item control page