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

• Published in: Scandinavian journal of rheumatology 2013-01, Vol.42 (3), p.215-219
• Main Authors: Große, K, Schmidt, RE, Witte, T, Baerlecken, NT
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Apoferritins - immunology; Autoantibodies - blood; Epitope Mapping; Female; Giant Cell Arteritis - blood; Giant Cell Arteritis - immunology; Humans; Male; Middle Aged; Polymyalgia Rheumatica - blood; Polymyalgia Rheumatica - immunology
• ISSN: 0300-9742; 1502-7732
• DOI: 10.3109/03009742.2012.733959

Objectives: 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). Method: 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. Results: 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. Conclusions: The potential diagnostic test for GCA/PMR can be improved by combining three human ferritin peptide antibodies.