Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.
A patient presenting delayed umbilical cord detachment, severe recurrent bacterial infections, and inability to form pus exhibited a profound defect in the expression of alpha- and beta-chains of the receptor for the C3bi fragment of C3 (CR3), lymphocyte function antigen 1 (LFA-1) molecule, and the p150,95 molecule found on neutrophils, monocytes, and lymphocyte membranes. This was shown by immunofluorescence studies using specific monoclonal antibodies, rosette formation with C3bi-coated erythrocytes, and immunoprecipitation for the LFA-1 complex. These membrane defects were responsible for abnormal phagocytic cell functions including adherence to nylon wool, cell movement, phagocytosis, and opsonized particle-induced oxidative response and for defective natural killer cell activity. In addition, lymphocyte function deficiencies previously unobserved in this disease were found. Cytolytic T lymphocyte activity was profoundly reduced; alpha- and gamma-interferon production were impaired. Finally, there was no antibody production to vaccinal antigens whereas the antibody responses to polysaccharides and to cytomegalovirus were found to be normal. The cytotoxic T cell deficiency could be expected from previous blocking experiments of this function with monoclonal antibodies to LFA-1 and is probably related to an extremely severe deficiency in LFA-1 expression in this patient. Anomalies in interferon and in antibody production suggest additional role(s) of the LFA-1 complex in monocyte/T lymphocyte/B lymphocyte cell interactions that have not yet been envisaged.
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis / Q000172:deficiency*; D001424:Bacterial Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D001770:Blood Bactericidal Activity; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000172:deficiency*; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D008214:Lymphocytes / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency; D009504:Neutrophils / Q000502:physiology; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis; D011951:Receptors, Complement / Q000172:deficiency*; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D012008:Recurrence; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D011951:Receptors, Complement; D011961:Receptors, Fc; D017452:Receptors, IgG