Leucocyte adhesion deficiency—A multicentre national experience

Baruch Wolach, Ronit Gavrieli, Ofir Wolach, Tal Stauber, Omar Abuzaitoun, Amir Kuperman, Yaakov Amir, Polina Stepensky, Raz Somech, Amos Etzioni

Research output: Contribution to journalArticlepeer-review

Abstract

Leucocyte adhesion deficiency (LAD) is a rare, innate autosomal recessive immunodeficiency with three subtypes. Twenty-nine patients with LADs were diagnosed and treated in Israeli Medical Centers and in the Palestinian Authority. We discuss the phenotypic, genotypic and biochemical features of LAD-I, LAD-II and LAD-III diagnosed during the neonatal period and early infancy in 18, 6 and 5 patients, respectively. Consanguinity was frequent. Common features were severe infections of variable aetiology, excessive leukocytosis and delayed umbilical cord detachment. In LAD-I, the integrin CD18 expression varied from negligible to normal. However, CD11a expression was negligible in all tested patients, suggesting both CD11a and CD18 should be used to assess this subtype. LAD-II patients showed distinctive facial features, physical malformations, short stature and developmental delay. These patients show defective expression of SLeX (CD15a) on cell surface glycoproteins and lack of H antigen on erythroid cell surfaces resulting in Bombay blood group (hh). LAD-III showed intact but inactive β2 integrins associated with severe infections and significant bleeding disorders caused by defective platelet aggregation and thrombocytopenia. We report four patients with two new unpublished mutations: two LAD-I patients with c.1099delG in ITGB2 and two LAD-III patients with c.1069C>T in FERMT3. LAD-I patients harbouring the c.119_128 deletion in ITGB2 seemed to have better outcomes as compared to other LAD-I patients. Eight patients with LAD-I and -III underwent successful haematopoietic stem cell transplantation. Cumulative survival was 75%, 50% and 40% for LAD-I, LAD-II and LAD-III, with a median follow-up of 4 (0.08-19), 3.25 (1-32) and 6 (0.08-8) years, respectively. Prenatal diagnosis is recommended in families with LAD syndromes.

Original languageEnglish
Article numbere13047
JournalEuropean Journal of Clinical Investigation
Volume49
Issue number2
DOIs
StatePublished - Feb 2019

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