Substances reactive with mannose-binding protein (MBP) in sera of patients with rheumatoid arthritis

OBJECTIVES: In order to evaluate the role of mannose-binding protein (MBP) in rheumatoid arthritis, we characterized MBP-binding substances in sera of patients with this disease. METHODS: An enzyme linked immunosorbent assay (ELISA) was used to detect MBP-binding substances in sera of patients with RA. We applied the sera of two RA patients to an immobilized MBP column, and by means of both ELISA and molecular sieve chromatography, examined the substances that bound to MBP. MBP-MASP complexes were added to the fractions containing the binding substances, and C4-consuming activity was examined. RESULTS: Sera of patients with RA showed stronger MBP binding on ELISA than did those of normal controls. In the case of RA sera, both IgG was IgM-RF eluted from the MBP column, whereas with normal controls, only IgG was obtained. The results of molecular sieve chromatography showed that the binding substances of RA patients consisted of immune complexes containing IgG and IgM-RF. These substances were specifically bound to MBP, and once bound, the MBP-MASP complexes were then able to consume C4. CONCLUSION: MBP binds to immune complexes consisting of IgG and IgM-RF, and probably recognizes either the mannose moiety of IgM-RF or the N-acetyl-glucosamine of agalactosyl IgG. When this occurs in RA patients, the lectin pathway would then be activated.