Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis.
OBJECTIVE
Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA. This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein. To investigate a potential correlation between the high levels of anti-LTSRPA antibodies in sera of patients with rheumatoid arthritis (RA) and the perpetuation of the immune response characteristic of this disease, we analyzed their capacity to activate complement and the process of binding to the serum lectin mannan binding protein (MBP).


METHODS
We used a radioimmunoassay to evaluate immune complexes between anti-LTSRPA IgG and FN, plasmin degraded FN, or the LTSRPA peptide for their capacity to activate complement C5 to C5a. Purified human serum lectin MBP was used to quantify the degree of exposed mannose or N-acetylglucosamine residues in the Fc region of anti-LTSRPA IgG of patients with RA and healthy controls.


RESULTS
Anti-LTSRPA IgG from patients with RA have a greater capacity to activate complement C5 to C5a when bound to either the LTSRPA peptide or plasmin degraded FN in vitro. We found a very strong correlation between the complement activating capacity of the RA immune complexes and their binding to MBP.


CONCLUSIONS
The enhanced capacity of RA anti-LTSRPA IgG immune complexes to activate complement C5 to C5a is directly correlated with their binding capacity to MBP. As MBP binding depends on exposed mannose or N-acetylglucosamine residues in the Fc region of the IgG molecule, these studies suggest that defective glycosylation of circulating anti-SK IgG may play a role in the etiology of RA.
Cuchacovich
M
M
Department of Medicine, Clinical Hospital-University of Santiago, Chile.
Gatica
H
H
Grigg
D M
DM
Pizzo
S V
SV
Gonzalez-Gronow
M
M
D000328:Adult; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity*; D008297:Male; D008351:Mannans / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D013300:Streptokinase / Q000276:immunology*
D001323:Autoantibodies; D002352:Carrier Proteins; D003182:Complement C5; D005353:Fibronectins; D007074:Immunoglobulin G; D008351:Mannans; D013300:Streptokinase