LEUKOCYTE ADHESION DEFICIENCY TYPE-1 (LAD-1) VARIANT - A NOVEL IMMUNODEFICIENCY SYNDROME CHARACTERIZED BY DYSFUNCTIONAL BETA(2) INTEGRINS/

Leukocyte adhesion deficiency (LAD) is characterized by the inability of leukocytes, in particular neutrophilic granulocytes, to emigrate fr om the bloodstream towards sites of inflammation, Infectious foci are nonpurulent and may eventually become necrotic because of abnormal wou nd healing, LAD-1 is characterized by the absence of the beta(2) integ rins (CD11/CD18) on leukocytes. When expression is completely absent, patients often die within the first year, However, low levels of beta( 2) expression may result in a milder clinical picture of recurrent inf ection, which offers a better prognosis. In this paper, we describe th e in vivo and in vitro findings on a patient with clinical features of a mild LAD-1 disorder, i.e., suffering from bacterial infections with out apparent pus formation in the presence of a striking granulocytosi s, showing no delayed-type hypersensitivity reaction upon skin testing , no specific antibody generation, but normal in vitro T cell prolifer ation responses after immunization. Expression levels of CD11/CD18 pro teins were completely normal, but leukocyte activation did not result in CD11/CD18 activation and high-avidity ligand-binding. In vitro chem otaxis and endothelial transmigration of the neutrophils as well as le ukocyte aggregation responses were almost absent. On the other hand, b eta(1) and beta(3) integrin-mediated adhesion functions were completel y normal. During follow-up, a bleeding tendency related to decreased b eta(3) activation became clinically apparent, different from previousl y described cellular adhesion molecule variants. Therefore, this is th e first well-documented case of a clinical combined immunodeficiency s yndrome that results from nonfunctional CD11/CD18 molecules, and thus designated LAD-1/variant.