Mononuclear phagocyte function in SLE. I. Bipartite Fc- and complement-dependent dysfunction.
To determine the relative contributions of Fc- and complement-mediated immune clearance to the overall mononuclear phagocyte system (MPS) dysfunction in SLE, we performed a kinetic analysis of clearance rate data from 32 patients and 49 normal controls. Three rate constants regulating complement-mediated MPS clearance and one rate constant regulating Fc-mediated MPS clearance were evaluated. Mean values for rate constants regulating complement-mediated phagocytosis (k4) and Fc-mediated clearance (k3) were significantly lower for the patient population as a whole when compared with normal controls (p less than 0.01 and p less than 0.001, respectively). Further analysis by clinical subgroups revealed that mean k3 values were significantly low for all but the inactive nonrenal subset of patients, whereas mean k4 values were significantly low for both the active and inactive renal patients but not for nonrenal patients. Rate constant values for Fc-mediated clearance correlated significantly with disease activity scores for the entire SLE group (p less than 0.001) as well as for the subset of patients with active and inactive renal disease (p less than 0.001). Neither k3 nor k4 correlated significantly with anti-DNA antibody, titers, total hemolytic complement levels, or circulating immune complexes. These data indicate that both Fc- and complement-mediated clearance defects occur in SLE. Nonrenal patients have at least one clearance mechanism intact, whereas immune complex glomerulonephritis is associated with dysfunctions in both of these clearance mechanisms.
D000328:Adult; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000502:physiology*; D007128:Immunoglobulin Fragments / Q000502:physiology*; D007074:Immunoglobulin G / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D010587:Phagocytosis; D012204:Rh-Hr Blood-Group System / Q000276:immunology; D018029:Rho(D) Immune Globulin
D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007136:Immunoglobulins; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; D003165:Complement System Proteins