*equally contributed
Introduction: Leukocyte Adhesion Deficiency 1 (LAD1) is an autosomal recessive primary immunodeficiency, hallmarked by defective PMN transmigration.It is caused by mutations in the CD18 gene, which interfere with the CD18/CD11 heterodimerization and expression on leukocyte cell surface. The aim of this study was to describe a group of LAD1 patients, their clinical presentation, inherited genetic mutations and laboratory findings, particularly cellular expression of the CD18/CD11 heterodimer.
Methods: Ten LAD1 patients diagnosed at the "Edmond and Lily Safra" Children`s hospital, Sheba Medical Center, Israel, between the years 2008 and 2013, were investigated. Genetic evaluation was performed and fluor-labeled antibodies aimed at CD18, CD11a, CD11b and CD11c were used in order to measure their cell surface expression using Flow Cytometry.
Results: Ten patients were studied, of which 7 were male. Seven patients presented with omphalitis during the newborn period. Four different mutations in the CD18 coding region were found. While levels of CD 18 expression ranged from absent to normal, all patients had absent or critically diminished levels of CD11a expression. Six patients remain on prophylactic antibiotics, one died and three underwent HSCT, of which two have since been clinically healthy with increased levels of CD11a and one rejected the transplant.
Discussion: Undetectable leukocyte CD11a expression, universal among our cohort of LAD1 patients, may provide an important tool for LAD1 diagnosis and monitoring following HSCT. As some of the reported mutations in CD18 are known to cause its impairment without markedly diminishing its expression,absent CD11a expression on the surface of PMNs could provide a valuable surrogate marker for defective CD18.
