Epitope mapping of antibodies against ferritin heavy chain in giant cell arteritis and polymyalgia rheumatica

Department of Immunology and Rheumatology, Medical University Hannover , Germany.
Scandinavian journal of rheumatology (Impact Factor: 2.53). 05/2013; 42(3):215-219. DOI: 10.3109/03009742.2012.733959
Source: PubMed


In a previous study we found an association between antibodies against the human ferritin heavy chain (HFC) protein and giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR), especially in GCA/PMR patients prior to glucocorticoid treatment. Antibodies against the N-terminal part of ferritin were present in 92% of untreated patients, 69% of patients with disease flare, and 13% of patients in remission. These antibodies appeared to be markers for the early detection of a disease complex usually diagnosed with considerable delay. Our aim in this study was to optimize the diagnostic test by epitope mapping of antibodies against HFC using peptide antigens in enzyme-linked immunosorbent assays (ELISAs).

We evaluated serum samples from a selected group of GCA/PMR patients in whom the sensitivity of antibodies against the N-terminal ferritin peptide was only 35%. Patients with late-onset rheumatoid arthritis (LORA), patients with fever, patients with granulomatosis with polyangiitis (GPA), patients without any autoimmune disease at age > 65 years, and blood donors served as controls.

By combining different ELISAs we were able to increase the frequency of human ferritin peptide antibodies in GCA/PMR (p < 0.0001) without significantly altering the false-positive rate (FPR) of the diagnostic test. The frequency of antibodies against human ferritin peptide increased from 53% to 74% in GCA/PMR patients with disease flare, from 29% to 40% in GCA/PMR patients in partial remission, and from 8% to 45% in GCA/PMR patients in complete remission.

The potential diagnostic test for GCA/PMR can be improved by combining three human ferritin peptide antibodies.

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    ABSTRACT: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely related diseases in people aged 50 years and older, which are more frequently observed in Western countries. Despite being common entities, concern still exists about the epidemiology, pathogenesis, and diagnosis of both entities. New imaging techniques, such as 18 fluorodeoxyglucose-positron emission tomography, have proved to be useful in detecting large-vessel involvement in GCA. Corticosteroids are the cornerstone of the therapy in GCA and PMR. Relapses are frequent in these conditions. Unlike methotrexate and tumor necrosis factor-α antagonists, anti-interleukin-6 receptor therapy appears to be useful in patients with GCA and PMR who are refractory to corticosteroids. This review summarizes recent studies on GCA and PMR.
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