Biomaterial Database

Mononuclear phagocyte system in SLE. II. A kinetic model of immune complex handling in systemic lupus erythematosus. 1986

N L Meryhew, and R P Kimberly, and R P Messner, and O A Runquist

Using the principles of reaction kinetics, we constructed a model for the handling of immune complexes and the pathogenesis of SLE immune complex disease. The model incorporates rate constants for complement- and Fc-mediated clearance, parameters for autoantibody, complement and immune complex levels, and scores for clinical disease activity. The model assumes that complement fixation by immune complexes is a prerequisite for complement-mediated clearance and that disease activity results from immune complex deposition. To test the relationships derived, data from 32 lupus patients were analyzed and the predictions were compared with actual findings. The model predicts a low correlation coefficient between disease activity and immune complex levels (found, r = 0.25, p greater than 0.1). The model also predicts a poor correlation between disease activity and impaired Fc-mediated clearance in patients with normal complement levels (found, r = 0.10, p greater than 0.1), but a high correlation coefficient between disease activity and impaired Fc-mediated clearance in patients with hypocomplementemia (found, r = 0.61, p less than 0.001). In patients with normal complement levels, the model predicts a good correlation between anti-DNA antibody and immune complex levels (found, r = 0.71, p less than 0.001), whereas hypocomplementemic patients should have a good correlation between anti-DNA to CH50 ratios and immune complex levels (found, r = 0.73, p less than 0.001). The model predicts that disease activity should correlate better with the product of the anti-DNA to CH50 ratio and the rate constant for Fc-mediated clearance than with any single parameter (found, r = 0.85, p less than 0.0001). These significant correlations, which were predicted by the model, suggest that complement-mediated mechanisms are the first line of host defense against immune complex-induced injury, that the efficiency of complement opsonization plays a central role, and that both abnormal complement- and Fc-receptor function leads to active renal disease in SLE.

UI	MeSH Term	Description	Entries
D007141	Immunoglobulin Fc Fragments	Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.	Fc Fragment,Fc Fragments,Fc Immunoglobulin,Fc Immunoglobulins,Ig Fc Fragments,Immunoglobulin Fc Fragment,Immunoglobulins, Fc,Immunoglobulins, Fc Fragment,Fc Fragment Immunoglobulins,Fc Fragment, Immunoglobulin,Fc Fragments, Ig,Fc Fragments, Immunoglobulin,Fragment Immunoglobulins, Fc,Fragment, Fc,Fragments, Ig Fc,Immunoglobulin, Fc
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008180	Lupus Erythematosus, Systemic	A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.	Libman-Sacks Disease,Lupus Erythematosus Disseminatus,Systemic Lupus Erythematosus,Disease, Libman-Sacks,Libman Sacks Disease
D008297	Male		Males
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009000	Monocytes	Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.	Monocyte
D010587	Phagocytosis	The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).	Phagocytoses
D003165	Complement System Proteins	Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).	Complement Proteins,Complement,Complement Protein,Hemolytic Complement,Complement, Hemolytic,Protein, Complement,Proteins, Complement,Proteins, Complement System
D005260	Female		Females