Deficiency in C3b receptors on neutrophils of patients with chronic granulomatous disease and hyperimmunoglobulin-E recurrent infection (Job's) syndrome.
C3b receptor (CR1) expression by neutrophils (PMNs) and erythrocytes (Es) from patients with chronic granulomatous disease (CGD) or with hyper-IgE, frequent infection (Job's) syndrome was compared with that of control subjects. The control subjects consisted of one group of patients with infections and a second group of normal, healthy individuals. Three quantitative assays were used: rosette formation with C3b-coated cellular intermediates (EAC43b), binding of radiolabeled monoclonal anti-CR1 ([125I]anti-CR1) to PMN surfaces, and binding of the antibody to nonidet P-40 (NP-40) extracts of PMNs and Es in an immunoradiometric assay. Rosette formation by the PMNs of five male CGD patients was about 50% of that of paired normal control subjects, whereas the rosette formation of three female CGD patients was similar to that of the control subjects. Surface binding of [125I]anti-CR1 to PMNs of 10 CGD patients was about half that of the normal subjects (mean percent binding was 2.33% for the CGD patients vs. 3.86% for the normal subjects, giving a difference of -1.53 +/- 0.22%, P less than 0.001 by the paired-sample t test). The degree of PMN binding was similarly low for both the male and the female CGD patients. Conversely, the binding of anti-CR1 to the PMNs of 11 infected control patients appeared to be similar to that of the normal subjects (4.51% for the patient vs. 4.21% for the paired normal subjects). The infected control group originally included four Job's syndrome patients, and when this subgroup was analyzed separately, their PMNs were shown to bind significantly less anti-CR1 than did the PMNs of the normal subjects (P less than 0.01 by the paired-sample t test). In contrast, the other infected control patients showed higher-than-normal levels of anti-CR1 binding (P less than 0.05). When compared to that of the normal subjects, the total CR1 quantitated in PMN extracts was also lower than normal in CGD patients (P less than 0.01 and in the PMN extracts of eight Job's syndrome patients tested (P less than 0.01). The PMNs of the other infected control subjects were not significantly different from those of the normal subjects in total CR1 expression. Extracts of Es from Job's syndrome patients also had fewer than normal CR1 (P less than 0.02). On the other hand, CR1 levels in E extracts from the CGD patients and the other control patients were similar to those in the normal control subjects. Quantitations of C3, C4, and factor B were normal in CGD.(ABSTRACT TRUNCATED AT 400 WORDS)
D000936:Antigen-Antibody Complex / Q000032:analysis; D003166:Complement Activating Enzymes / Q000378:metabolism; D015922:Complement C1q; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000097:blood*; D006801:Humans; D007589:Job Syndrome / Q000097:blood*; D008297:Male; D009504:Neutrophils / Q000032:analysis*; D010585:Phagocyte Bactericidal Dysfunction / Q000097:blood*; D011863:Radioimmunoassay; D011951:Receptors, Complement / Q000032:analysis* / Q000276:immunology; D017463:Receptors, Complement 3b; D012397:Rosette Formation; D012737:Sex Factors
D000936:Antigen-Antibody Complex; D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D015922:Complement C1q; D003166:Complement Activating Enzymes