In patients with rheumatoid arthritis IgG binding to denatured collagen type II is in part mediated by IgG-fibronectin complexes.
The presence of autoantibodies to native and denatured collagen type II has been reported in some patients with rheumatoid arthritis (RA). This study examined the molecular nature of IgG binding to native and denatured collagen type II. The binding of IgG to native and denatured collagen was detected with an ELISA. Serum proteins were separated by size with gel filtration. Gel-filtered fractions were further characterized by binding to staphylococcal protein A. Among plasmas or serums from 60 patients with RA, 12 patients had IgG binding to native collagen type II and 12 had IgG binding to denatured collagen type II. Decomplementing normal serums by heating to 56 degrees C for 30 min markedly increased IgG binding to denatured collagen type II, but not to native collagen. This binding was shown to result from a complex formed between IgG and fibronectin. Nine unheated RA serums were separated by gel filtration. The IgG binding to native collagen was limited to monomeric IgG, but in these serums 65.6 +/- 22.0% of the IgG binding to denatured collagen type II was in the excluded protein fractions. The binding of IgG to denatured collagen type II in the excluded fractions was inhibited by fibronectin and did not bind to staphylococcal protein A. In patients with RA, the IgG binding to native collagen type II represents true autoantibodies. In contrast, in these patients the majority of IgG binding to denatured collagen type II is caused by macromolecular complexes formed between fibronectin and IgG or between fibronectin and IgG-containing immune complexes.
Mannik
M
M
Division of Rheumatology, Department of Medicine, University of Washington, Seattle 98195, USA.
Kapil
S
S
Merrill
C E
CE
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D046911:Macromolecular Substances; D011485:Protein Binding; D011489:Protein Denaturation
D005353:Fibronectins; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D003094:Collagen