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THU0224 Prevalence of antibodies against ferritin peptides: Epitope mapping of human ferritin heavy chain in GCA and PMR
  1. N.T. Baerlecken,
  2. K. Große,
  3. R.E. Schmidt,
  4. T. Witte
  1. Department of Clinical Immunology and Rheumatology, Medical University Hannover, Hannover, Germany

Abstract

Background In a previous study, we investigated the prevalence of autoantibodies against the human ferritin heavy chain protein (HFC) in sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) (1). Their sensitivity was 92% in untreated, but only 15% in treated and inactive patients.

Objectives To optimize this potential diagnostic test of GCA/PMR by an epitope mapping of HFC.

Methods Six ELISAs with six different peptides of HFC as an antigen were established. As autoantigen we used the full recombinant HFC expressed by E. coli or one of six different peptides of the HFC: 1-18Aa MTTASTSQVRQNYHQDSE (purity 98.8%), 19-45Aa AAINRQINLELYASYVYLSMSYYFDRD (purity 98.8%), 52-78Aa FAKYFLHQSHEEREHAEKLMKLQNQRG purity 98.3%), 79-104Aa GRIFLQDIKKPDCDDWESGLNAMECA (purity 98.8%), 105-143Aa LHLEKNVNQSLLELHKLATDKNDPHLCDFIETHYLNEQVK (purity 98.4%), 145-183Aa AIKELGDHVTNLRKMGAPESGLAEYLFDKHTLGDSDNES (purity 98.5%). 70 GCA/PMR sera were tested consisting of 25 patients positive for HFC autoantibodies and 45 patients negative for HFC autoantibodies. 49 sera of fever patients, 31 sera of patients with late onset rheumatoid arthritis and blood donors’ sera served as controls.

Results By combining different ELISAs for autoantibodies against 19-45Aa, 79-104Aa and 105-143Aa, we were able to increase the frequency for all large vessel vasculitis diseases from 25/70 (34%) in previous antibody negative sera to 46/70 (66%) (p<0.0001) without decreasing severly false positive rate of the diagnostic test. The frequency increased from 53% to 74% in GCA and PMR patients with disease flare, from 29% to 40% in GCA and PMR patients in partial remission and from 8% to 45% in GCA and PMR patients in complete remission.

Conclusions Autoantibodies against different peptides of HFC are valuable markers for early diagnosis for GCA and PMR and may even be useful for verification of the diagnosis after 3 years of treatment.

  1. Baerlecken NT, Linnemann A, Gross WL, Moosig F, Vazquez-Rodriguez TR, Gonzalez-Gay MA, Martin J, Kötter I, Henes JC, Melchers I, Vaith P, Schmidt RE, Witte T. Association of ferritin autoantibodies with giant cell arteritis/polymyalgia rheumatica. Ann Rheum Dis. 2012 Jan 5. [Epub ahead of print]

Disclosure of Interest None Declared

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