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Review
. 2019 Aug 7;7(1):107-114.
doi: 10.1016/j.gendis.2019.07.012. eCollection 2020 Mar.

Leukocyte adhesion defect: Where do we stand circa 2019?

Jhumki Das  1 , Avinash Sharma  2 , Ankur Jindal  1 , Vaishali Aggarwal  1 , Amit Rawat  1
Affiliations
Review

Leukocyte adhesion defect: Where do we stand circa 2019?

Jhumki Das et al. Genes Dis. .

Abstract

Migration of polymorphonuclear leukocytes from bloodstream to the site of inflammation is an important event required for surveillance of foreign antigens. This trafficking of leukocytes from bloodstream to the tissue occurs in several distinct steps and involves several adhesion molecules. Defect in adhesion of leukocytes to vascular endothelium affecting their subsequent migration to extravascular space gives rise to a group of rare primary immunodeficiency diseases (PIDs) known as Leukocyte Adhesion Defects (LAD). Till date, four classes of LAD are discovered with LAD I being the most common form. LAD I is caused by loss of function of common chain, cluster of differentiation (CD)18 of β2 integrin family. These patients suffer from life-threatening bacterial infections and in its severe form death usually occurs in childhood without bone marrow transplantation. LAD II results from a general defect in fucose metabolism. These patients suffer from less severe bacterial infections and have growth and mental retardation. Bombay blood group phenotype is also observed in these patients. LAD III is caused by abnormal integrin activation. LAD III patients suffer from severe bacterial and fungal infections. Patients frequently show delayed detachment of umbilical cord, impaired wound healing and increased tendency to bleed. LAD IV is the most recently described class. It is caused by defects in β2 and α4β1 integrins which impairs lymphocyte adhesion. LAD IV patients have monogenic defect in cystic-fibrosis-transmembrane-conductance-regulator (CFTR) gene, resulting in cystic fibrosis. Pathophysiology and genetic etiology of all LAD syndromes are discussed in detail in this paper.

Keywords: Neutrophilic defect; Neutrophilic leukocytosis; Phagocyte rolling; Phagocytes; Primary immunodeficiency disorders.

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Figures

Figure 1
Figure 1
Showing a non-healing ulcer without pus over neck of a patient.
Figure 2
Figure 2
Palatal ulcer.
Figure 3
Figure 3
Flow-CytometricImmunophenotyping for CD18 Leukocytes on peripheral blood: neutrophil gated using SSC/FSC and CD18 expression is measured in (A) healthy control against (B) LAD patient. CD18 expression is normal in control while its absent in the patient.
See this image and copyright information in PMC

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