Effect of polymorph derived oxidants on IgG in relation to rheumatoid factor binding.
Immunoglobulin G from rheumatoid patients is denatured around the hinge region. This has been proposed as an explanation for the presence of circulating autoantibodies to IgG in these patients. It has previously been suggested that oxygen radicals (OR) derived from activated polymorphs may play a role in denaturation in vivo. Using sera from rheumatoid patients and age-matched controls in a modified ELISA technique, we have investigated the potential for polyclonal rheumatoid factors (RF) to bind to OR denatured IgG. Three model systems were used to generate OR in vitro: (a) purified PMN s activated by the cell surface stimulant PMA, (b) radiolysis of IgG in solution to generate specifically the superoxide radical and, in a separate system, the hydroxyl radical, (OH.), (c) purified myeloperoxide in the presence of H2O2 and halide ions.


RESULTS
1. The binding of both IgA and IgM RF s to PMN denatured IgG increased dose dependently for seropositive sera only. 2. The OH. radical but not the superoxide radical significantly increased the binding of IgA and M RF, again only for seropositive sera. 3. The myeloperoxidase enzyme system did not increase RF binding. 4. IgG incubated with elastase was not found to be a better antigen than native IgG. These results indicate that IgG is denatured by OR released from activated PMN, thereby producing an antigen for polyclonal RF s.
Griffiths
H R
HR
Department of Biochemistry, Selly Oak Hospital, Birmingham, UK.
Lunec
J
J
D001172:Arthritis, Rheumatoid / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005609:Free Radicals; D005720:Gamma Rays; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D012217:Rheumatoid Factor / Q000276:immunology*; D013481:Superoxides / Q000502:physiology
D005609:Free Radicals; D007074:Immunoglobulin G; D013481:Superoxides; D012217:Rheumatoid Factor; D010100:Oxygen