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Leukocyte Adhesion Deficiency Types II and III

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P730-731

2026-07-22

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 LAD type II is a very rare clinical syndrome closely related to LAD I but caused by a defect in selectin-mediated adhesion events from a deficiency in leukocyte sialyl-Lewis X ligands. It was first reported by Etzioni et al. in two unrelated boys of Muslim Arab origin and has since been described in a total of five individuals (four Arab and one Turkish). The disease is inherited in an AR manner. Patients present with neutrophilia, recurrent bacterial infections, and periodontitis, similar to LAD I, although these symptoms were generally not as severe. In addition, LAD II is associated with dysmorphic features and psychomotor retardation. LAD II neutrophils express normal levels of CD18. A clue as to the molecular cause of LAD II came from the observation that LAD II red cells were Lewis anti gen–negative and also had the rare Bombay (hh) erythrocyte phenotype, in which red blood cells express a nonfucosylated variant of the H antigen. These antigenic defects share in common the failure to form certain fucose carbohydrate linkages. The defect in fucose metabolism in LAD II has now been shown to result from mutations in the Golgi guanosine diphosphate–fucose membrane transporter. This leads to a generalized loss of expression of fucosylated glycans on the surface of cells, particularly the sialylated and fucosylated tetrasaccharide, SleX (CD15a), on the neutrophil surface. As a result, LAD II neutrophils are unable to bind to E- and P-selectin receptors on endothelium and therefore have an impairment in the early steps of rolling and loose binding to blood vessel walls before tight adhesion and emigration into infected tissues. Fucose supplementation has been partially successful in increasing expression of SLeX and decreasing clinical problems.

LAD type III has been described in a handful of patients with severe, recurrent infections similar to LAD I, as well as a bleeding tendency similar to Glanzmann thrombasthenia (a β3 integrin–related disorder). This disorder results from AR defects in KINDLIN-3, a regulatory protein required for “inside-out” activation of multiple classes of integrins in blood cells. Because the clinical manifestations are typically severe, early BMT may be indicated for patients with LAD III.