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This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

Antibodies to ferritin in rheumatoid arthritis are associated with disease severity

D Mewar1, DJ Moore2, PF Watson3 and AG Wilson1

Author Affiliations

1 Division of Genomic Medicine, University of Sheffield, UK

2 Department of Radiology, Royal Hallamshire Hospital, Sheffield, UK

3 Division of Clinical Sciences North, University of Sheffield, UK

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Arthritis Research & Therapy 2005, 7(Suppl 1):P128  doi:10.1186/ar1649

The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Background and objectives

A number of autoantibodies have been described in individuals with rheumatoid arthritis (RA) leading to interest in their use as diagnostic or prognostic markers in RA as well as their pathogenic relevance. By immunoscreening of a phage-display expression cloning system with RA patient sera we isolated a cDNA clone encoding the ferritin H chain polypeptide. The objectives of this study were to establish the frequency and clinical associations of anti-ferritin antibodies in RA.

Methods

We employed an ELISA for the measurement of anti-ferritin antibodies in RA sera. Briefly, 96-well plates were coated overnight with purified ferritin from equine spleen. Sera diluted one in 100 were reacted with the plates for 16 hours at 4°C. After three washes, a goat anti-human IgG/horseradish peroxidase conjugate was used to detect bound IgG. The signal for each serum sample was normalised using a reference serum included on each plate. Anti-ferritin antibodies were measured in 291 subjects with RA, 73 healthy blood donors and 91 subjects with osteoarthritis. Antibody-positive and antibody-negative individuals were compared with respect to severity of disease as measured by modified Larsen's score, demographic variables, rheumatoid factor status and carriage of HLA DRB1 shared epitope alleles. Correlations were examined between antibody levels and severity of joint damage assessed by the Modified Larsen's score.

Results

Using a cut-off index of three standard deviations above the mean of the control group, 49/291 (16.8%) RA patients were positive versus 2/73 (2.7%) healthy donors and 2/91 subjects with osteoarthritis (P < 0.01). In six positive and six negative sera these findings were confirmed by western blotting. Anti-ferritin antibodies were more common in males with RA (25.3% males versus 13.7% females, P < 0.02) and levels were positively associated with severity of joint damage (rs = 0.33, P = 0.02).

Conclusions

Anti-ferritin antibodies are present in a subset of individuals with RA and are associated with more severe joint damage. Ferritin is an abundant protein in serum and synovial fluid, and therefore ferritin/anti-ferritin immune complexes could form in these individuals and contribute to joint damage. An alternative possibility is that anti-ferritin antibodies could modulate the iron-binding properties of ferritin and so lead to the release of toxic-free iron in the joint. We are currently examining the frequency of anti-ferritin reactivity in patients with early RA at two timepoints in order to establish whether or not these antibodies are present in early disease or are simply a result of longstanding disease, as well as their frequency in other autoimmune diseases. These data will be presented.