Ferritin concentrations in synovial fluid are higher in osteoarthritis patients with HFE gene mutations (C282Y or H63D)

Abstract

Objectives: In view of the clinical similarities between polyarticular osteoarthritis (POA) with metacarpophalangeal (MCP) joint involvement and the arthropathy that occurs in hereditary haemochromatosis (HH), it was hypothesized that osteochondral damage in both disorders may be due to localized iron overload. Accordingly, it was predicted that the concentration of ferritin in synovial fluid (SF) would be higher in OA patients with HFE gene mutations than in HFE wild-type (wt) OA patients. The aim of this study was to test this proposition.

Methods: Sequential patients with physician-diagnosed OA and, for comparison, diverse inflammatory diseases of the joints, who required diagnostic or therapeutic arthrocentesis, were studied. Participants underwent HFE genotyping. SF samples were assayed for ferritin and also for selected cytokines and matrix metalloproteinases (MMPs).

Results: Seventy-three patients with diverse rheumatic disorders were recruited. Of the 29 patients who had knee OA, 15 were wt and 14 were heterozygous for HFE mutations (C282Y or H63D). Mean SF ferritin concentrations in the wt and heterozygous OA groups were 273 and 655 ng/mL, respectively (p = 0.0146).

Conclusions: A predicted difference in SF ferritin concentrations in patients with knee OA was confirmed. Concentrations of ferritin in the SF were found to be two- to threefold higher in knee OA patients with HFE gene mutations compared to wt patients. This finding is consistent with the possibility that, in OA patients with HFE gene mutations, localized iron overload may contribute either directly or indirectly to osteochondral damage, possibly in a similar way to that which occurs in the arthropathy that complicates HH.

Acknowledgements

We thank Dr Sydney Sacks from CliniPath Laboratories, the PathWest Laboratory staff at Fremantle Hospital, and Mr Robert Genat (Orthopaedic Surgeon) for their generous assistance with the collection and processing of synovial fluids. We are also indebted to Dr Shane Byrne, Sullivan Nicolaides Pathology, for the conduct of genotyping experiments and Bronwyn Carroll for data processing and graphics. This work was funded by generous contributions from the L.E.W. Carty Foundation, Melbourne, Australia and the Arthritis Foundation of Western Australia (ArthritisWA).