Deficiency of two human leukocyte surface membrane glycoproteins (Mo1 and LFA-1).
Structural and functional features of a novel disorder characterized by recurrent bacterial infections are reviewed. This disease is associated with a number of phagocyte adhesion defects. In 10 patients, phenotypic analysis with monoclonal antibodies (MAb) revealed the same basic defect in all patients: deficiency of at least two leukocyte surface glycoproteins, Mo1 and LFA-1. These two antigens have distinct alpha subunits (Mo1 alpha = 155 kilodaltons, LFA-1 alpha = 177 kilodaltons) noncovalently linked to a common beta subunit (94 kilodaltons). Mo1 is closely associated with or identical to a receptor for the iC3b fragment of the third component of complement. LFA-1 is involved in lymphocyte proliferation, cytotoxicity, and natural killing. MAb directed to this family of glycoproteins induce functional defects in normal cells similar to those observed in deficient cells. In normal cells, the surface expression of these glycoproteins is regulated by the state of cell activation. Mitogens and alloantigens significantly increase the surface expression of LFA-1 on T lymphocytes. Stimuli that induce degranulation in neutrophils increase the surface expression of Mo1. In all patients with combined Mo1, LFA-1 deficiency, the predominant clinical manifestations were more characteristic of a phagocyte than a lymphocyte disorder. In vitro studies, however, reveal significant defects in phytohemagglutinin-induced proliferation that are more apparent at lower concentrations of the lectin. In some families, more than one sibling is affected. Intermediate levels of Mo1 were observed on granulocytes from both parents of one child. In one family, however, only the mother had significantly reduced levels of Mo1, which indicates heterogeneity in the inheritance of this disorder.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1; D008214:Lymphocytes / Q000502:physiology; D016177:Macrophage-1 Antigen; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000276:immunology*; D051379:Mice / Q000276:immunology; D012397:Rosette Formation; D012756:Sheep / Q000276:immunology
D000954:Antigens, Surface; D001798:Blood Proteins; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen