Novel aspects of Kindlin-3 function in humans based on a new case of leukocyte adhesion deficiency III.

Journal of Thrombosis and Haemostasis : JTH
Julia MellerT V Byzova

Abstract

Kindlin-3 is a novel integrin activator in hematopoietic cells, and its deficiency leads to immune problems and severe bleeding, known as leukocyte adhesion deficiency III (LAD-III). Our current understanding of Kindlin-3 function primarily relies on analysis of animal models or cell lines. To understand the functions of Kindlin-3 in human primary blood cells. We analyzed primary and immortalized hematopoietic cells obtained from a new LAD-III patient with immune problems, bleeding, a history of anemia, and abnormally shaped red blood cells. The patient's white blood cells (WBCs) and platelets showed defects in agonist-induced integrin activation and botrocetin-induced platelet agglutination. Primary leukocytes from this patient exhibited abnormal activation of β(1) integrin. Integrin activation defects were responsible for the observed deficiency in the botrocetin-induced platelet response. Analysis of patient genomic DNA revealed a novel mutation in the Kindlin3 gene. The mutation abolished Kindlin-3 expression in primary WBCs and platelets, owing to abnormal splicing. Kindlin-3 is expressed in red blood cells (RBCs), and its deficiency is proposed to lead to abnormally shaped RBCs. Immortalized patient WBCs expressed a trunc...Continue Reading

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Citations

Oct 12, 2012·Journal of Clinical Immunology·Mohammad S EhlayelMohammad Abu Laban
Dec 5, 2012·Current Opinion in Hematology·Estelle S HarrisGuy A Zimmerman
Sep 23, 2014·Journal of Clinical Immunology·Amos Etzioni
Dec 21, 2012·Molecular Immunology·Sarah SchmidtMarkus Sperandio
Mar 15, 2014·Current Opinion in Hematology·Edward F PlowTatiana V Byzova
Jun 28, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhen XuYan-Qing Ma
Nov 15, 2019·Pediatric Blood & Cancer·Georgi ManukjanOliver Andres
Feb 7, 2020·Life Science Alliance·Katarzyna BialkowskaEdward F Plow
Feb 25, 2020·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Mohammed F EssaAbdulrahman Alsultan

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