title: Control of immune complexes by the classical pathway.
abstract: The association between inherited deficiencies of the classical pathway complement components (C1q, C1r, C1s, C4, C2 and C3) and immune complex disease shows that complement is involved in protection against the development of immune complex disease (ICD). This protection is conferred by the ability of the complement system to keep antigen antibody complexes (IC) small and soluble. Two mechanisms exist, prevention of immune precipitation (PIP), which inhibits the formation of large insoluble lattices when IC are formed in the presence of complement (nascent IC), and solubilisation of preformed immune precipitates (SOL). PIP is probably the more important as it is unlikely that, in vivo, IC are ever formed in the absence of complement. PIP displays an absolute dependency upon the classical pathway while SOL is alternative pathway dependent. However, for optimal efficiency SOL requires an intact classical pathway. Thus the classical pathway plays a role in both PIP and SOL. The end result of both processes is the covalent binding of C3b to the IC lattice, which not only keeps IC soluble, but permits binding to CR1 for removal from the circulation. The sera of patients with ICD contain a factor (s) which inhibits PIP. The sera of RA patients inhibits PIP and purified IgM-RF has been shown to inhibit this function. However a second inhibitor of PIP has recently been purified, a glycoprotein (Mr 60 kd) (gp60) which is present in normal serum and in increased concentration in RA sera. Gp60 binds to the Fc piece of IgG, but not to IgA or IgM, and competes with C1q for a binding site on IgG Fc. Thus gp60 appears to act by preventing binding and activation of C1 by IgG containing IC.
authors.affiliation: Department of Pathology, Western Infirmary, Glasgow, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Whaley
authors.forename: A E
authors.initials: AE
authors.lastname: Ahmed
mesh_terms: D000936:Antigen-Antibody Complex / Q000378:metabolism*; D011232:Chemical Precipitation; D003167:Complement Activation; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004198:Disease Susceptibility; D006801:Humans; D007105:Immune Complex Diseases / Q000235:genetics / Q000276:immunology*; D012995:Solubility
chemical_list: D000936:Antigen-Antibody Complex; D003165:Complement System Proteins