Moran, Jennifer Ann (2019) Investigation of serum monomeric C-reactive protein and associated auto-antibodies in rheumatoid arthritis. Doctoral thesis, Keele University.

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Abstract

The research described here considers molecular variations of the acute phase response protein, C reactive protein (CRP), and the presence of CRP and anti CRP autoantibodies in rheumatoid arthritis (RA) patient serum.
Monomeric CRP (mCRP) was generated in vitro by 2M urea induced dissociation of native pentameric CRP (pCRP), over a 10 week period in the absence of calcium. The subunit size (23kDa) and identity were confirmed by size exclusion chromatography, and western blotting with mCRP specific antibodies. Once dissociated, it was not possible to induce re-association.
Human RA (n=30) and healthy control samples (n=30) were tested for the presence of serum mCRP. RA patients had higher mean mCRP levels than non RA (0.092mg/l, 0.069mg/l), however no samples were elevated above the calculated normal threshold for mCRP (≥ mean + 2SD, 30 control samples). There was no correlation between serum levels of mCRP and pCRP, suggesting physiological dissociation of pCRP may not be solely responsible for the presence of mCRP.
Auto-antibody detection by competitive ELISA confirmed the presence of antimCRP and pCRP auto-antibodies of the classes IgG, IgA and IgM in both RA and control groups. Anti-mCRP and pCRP auto-antibodies in RA samples were significantly higher than controls in the female cohort in all but anti-mCRP IgM, with only anti-m/pCRP IgA significantly higher for the males (P<0.01). Both mCRP and pCRP were found to interact directly with anti-IgG at high concentrations of both. A greater proportion of RA samples contained all three auto-antibody classes, anti pCRP - RA 66.6%, control 50%; antimCRP- RA 50%, control 13%. Auto-antibody profile varied between RA and control groups, elevated anti-mCRP IgA antibodies being a key predictor of RA risk P<0.0001, more so when combined with advancing age although no correlation between CRP and auto-antibody concentrations was found. This may prove useful diagnostically.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Lisa Bailey
Date Deposited: 19 Mar 2019 10:41
Last Modified: 19 Mar 2019 10:41
URI: http://eprints.keele.ac.uk/id/eprint/6087

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