Hematologically Important Mutations: Leukocyte Adhesion Deficiency (Second Update) Publisher Pubmed



Roos D¹ ; Van Leeuwen K¹ ; Madkaikar M² ; Kambli PM² ; Gupta M² ; Mathews V³ ; Rawat A⁴ ; Kuhns DB⁵ ; Holland SM⁶ ; De Boer M¹ ; Kanegane H⁷ ; Parvaneh N⁸ ; Lorenz M⁹ ; Schwarz K^{9, 10} Show All Authors
Source: Blood Cells, Molecules, and Diseases Published:2023

Abstract

Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing, accompanied by neutrophilia. In LAD-I, characterized directly after birth by delayed separation of the umbilical cord, mutations are found in ITGB2, the gene that encodes the β subunit (CD18) of the β2 integrins. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Lea and Leb blood group antigens. Finally, in LAD-III, the conformational activation of the hematopoietically expressed β integrins is disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells, involved in the regulation of β integrin conformation. This article contains an update of the mutations that we consider to be relevant for the various forms of LAD. © 2023