Immune complex modulation by plasma proteins. With special reference to the complement system and autoimmune diseases.
The complement (C) system consists of two activation pathways, the classical and the alternative, which may both be activated by immune complexes (IC). C activation products become attached to the IC during activation leading to profound changes in the properties of the complexes. The common terminal C pathway is not involved in activation mediated by fluid phase IC. The interaction between IC and C may lead to: 1) Increased solubility of the IC. 2) Enhanced phagocytosis and clearance of the IC. 3) Altered tissue distribution of the IC. 4) Generation of soluble C fragments which mediate inflammation. 5) Tissue damage by activation and/or lysis of bystanding cells. 6) Modulation of B-cell proliferation and differentiation. Activation of the C system by IC is an essential normal component in the clearance of invading foreign material. However, in conditions with a persistent high concentration of IC in the circulation or tissues, this activation may lead to chronic inflammatory disease. This thesis reviews certain aspects of the interactions between IC and C. The earlier work describes our development of an assay for measuring the C activity in patient sera by its ability to solubilize preformed, fluid phase IC (CMS assay). The CMS was found to be dependent upon the alternative pathway of C and facilitated by the classical. Further studies concerning the influence of C deficiencies or depletion of C factors, the concentration of divalent metallions, the temperature and the ionic strength were performed to characterize the reaction. The CMS assay, showed that serum from patients with SLE and other systemic persistent inflammatory diseases and infections exhibited a reduced capacity to solubilize IC. The CMS values correlated inversely to the disease activity in SLE patients. It was also for the first time demonstrated that serum from some SLE patients contained a CMS inhibitor and it is suggested that this inhibitor of CMS is endogenously formed incompletely C solubilized IC. This suggestion is based upon several lines of indirect evidence, and by HPLC size distribution analysis of the IC in SLE sera, which showed a reduction in IC size upon incubation with C. A negative correlation between the CMS capacity and the content of CMS inhibitory material was found. The CMS capacity did not correlate to the serum concentration of any of the C factors C3b/C3c, C4, Clq, factor B, factor H or factor I, nor did it correlate to the concentration of the degradation product C3dg. But a low concentration of one of the native C factors was associated with a reduced CMS.(ABSTRACT TRUNCATED AT 400 WORDS)
Baatrup
G
G
Institute of Medical Microbiology, University of Odense.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002097:C-Reactive Protein / Q000502:physiology; D037222:Collectins; D003167:Complement Activation / Q000502:physiology*; D003170:Complement Pathway, Alternative / Q000502:physiology*; D003171:Complement Pathway, Classical / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology*; D037102:Lectins / Q000502:physiology; D012712:Serum Globulins / Q000502:physiology
D000936:Antigen-Antibody Complex; D037222:Collectins; D005353:Fibronectins; D037102:Lectins; D012712:Serum Globulins; C024014:conglutinin; D002097:C-Reactive Protein