title: Antibodies to C1q and C-reactive protein in autoimmune inflammatory disease
Creators: name: McBain, James
Publisher: name: University of Glasgow
Year: 2001
Subjects: subject: Immunology.

description: Background Patients with increased levels of autoantibodies often have associated inflammatory disease. Immune complexes are often seen in inflammatory disease. They may be formed by antibodies produced against the Clq molecule which has been altered by the inflammatory process, and also by antibodies produced against C reactive protein (CRP) plasma levels of which become greatly increased during inflammation. These immune complexes can induce complement consumption, resulting in low serum levels of complement components, leading to pathogenesis of chronic inflammation and inflammatory disease. Raised levels of C3d are an indicator of increased complement consumption. It is not known whether antibodies to Clq and/or antibodies to CRP are responsible for autoimmune inflammatory disease or whether they are produced as a result of the disease. Aims The aim of this thesis is to establish a link between levels of antibodies to Clq, antibodies to CRP, and inflammatory disease and thus provide evidence that these antibodies may be involved in the pathogenesis of chronic inflammation leading to inflammatory disease. This thesis tries to determine if (a) patients with inflammatory disease have a significantly different than normal level of antibodies to Clq, and of antibodies to CRP, and whether this depends on immunoglobulin isotype and type of inflammatory disease. Also investigated was (b) possible associations of antibodies to Clq, and/or antibodies to CRP with age and biological markers of autoimmune inflammatory disease. Another aim was (c) to determine if there were increased levels of C3d, an indicator of complement consumption, thus providing indirect evidence of the presence of immune complexes in patients with inflammatory disease. Subjects and Methods Patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and heterogenous autoimmune inflammatory disease (HAID) were tested for antibodies to Clq, antibodies to CRP, Clq levels and antibodies to double stranded DNA using enzyme-linked immunosorbent assay (ELISA) methods. Complement C3, C4 and Cl inhibitor levels were measured by nephelometry and antinuclear antibodies (ANA) by immunofluorence techniques. An ELISA method was developed to measure C3d levels in patients with SLE, renal disease and HAID. Results It was demonstrated that differences in antibody titres to Clq depend on the type of inflammatory disease and immunoglobulin isotype, and there is an association between antibody titres to Clq (of IgG, IgA and IgM isotype) and age and various biological markers of disease activity. Inflammatory disease appears to affect the complement levels of C3, C4 and Cl inhibitor. There is a direct link between increased antibody titres to CRP and inflammatory disease and IgG antibodies to CRP increase as C3 and C4 levels decrease. Also, patients with inflammatory disease have increased levels of C3d. Conclusions The results show there is strong evidence that antibodies to Clq and antibodies to CRP of certain immunoglobulin isotype (IgG, IgA and IgM) form immune complexes which induce complement consumption. The resulting complement deficiency would impair the ability of complement to clear immune complexes. An autoimmune response is then triggered and so the cycle goes on leading to chronic inflammation and inflammatory disease. Future studies should try to determine how and why this inflammatory cycle is initiated. Certainly, it appears that measurement of antibodies to CRP and possibly antibodies to Clq may prove to be a useful tool for diagnosing inflammatory disease.