Anti-BIP antibodies in rheumatoid arthritis

Background

We have implicated the human chaperone protein BiP in the pathogenesis of rheumatoid arthritis (RA). Increased immunoglobulin binding of RA sera to BiP is seen on Western blot analysis.

Methods

We now describe an ELISA developed to enable rapid screening of sera for antibody reactivity to BiP.

Results

Specificity of the assay has been shown by free ligand competition and extensive correlations with other immunological parameters. We show no correlation between anti-BiP and rheumatoid factor or with cyclic citrullinated peptide. We confirm the increased binding of immunoglobulin to BiP in the sera of a group of patients with RA (n = 96) in comparison with controls (n = 96). Our data show a specificity of 71% and a sensitivity of 73% for RA. Furthermore, these data show that antibody will bind to a nonglycosylated form of BiP, since the protein is produced in an Escherichia coli expression system.

Conclusion

We have developed a robust protocol for the detection of antibodies to the human chaperone molecule BiP. Our data show an elevated antibody response to BiP in RA patients and hence support a role for this molecule in the disease.