Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullina
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RESEARCH
Open Access
Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis Sanna Turunen1*, Marja-Kaisa Koivula1,2, Jukka Melkko3,4, Eeva Alasaarela5, Petri Lehenkari6,7 and Juha Risteli1,2
Abstract Background: Antibodies binding to citrullinated proteins are a frequent finding in rheumatoid arthritis patients and may precede the onset of clinical symptoms several years. The antibodies are a predisposing factor for bone erosions but their origin is unknown. In this study we analyze in detail the levels of protein bound citrulline and homocitrulline in several tissue samples of a single erosive arthritic surgery patient. Methods: Serum antibodies binding to CCP, MCV and citrulline- or homocitrulline-containing type I and II collagen carboxytelopeptides were measured. Tissue samples of a single RA patient, taken in two separate operations performed with two-year time span were hydrolyzed and analyzed for citrulline and homocitrulline content by HPLC. Results: Protein-bound citrulline and homocitrulline were found in several joint tissues of a RA patient with ACPApositive erosive disease. The amount of homocitrulline stayed relatively constant between the different tissues. The amount of citrulline in erosive tissue was 3-times higher than in non-erosive tissue in the first operation. In the samples of the second operation 3-4-times higher mean amounts of citrulline were found in two out of the six tissues investigated. Conclusions: Homocitrulline is present in rheumatoid nodule together with citrulline. There is more variation in the amount of citrulline than in the amount of homocitrulline between the tissues. The tissue sample containing the most citrulline was the most erosive. Keywords: Citrulline, Homocitrulline, Rheumatoid arthritis, Autoantibodies, Tissue, Carbamylation
Background Antibodies binding to citrullinated proteins are a frequent finding in rheumatoid arthritis (RA) patients and may precede the onset of clinical symptoms several years [1]. The anti-citrullinated protein antibodies (ACPA) are a predisposing factor for bone erosions in RA patients [2]. The ACPA antibody repertoire of RA patients has been quite specifically characterized [3-5] and possible candidate antigens for these antibodies have also been demonstrated in several studies [6-8]. Antibodies binding
to carbamylated proteins have been found recently in RA sera [9] but the presence of homocitrulline-containing proteins in RA tissues have not been demonstrated yet. Recent studies on RA have suggested that the original antigen of ACPA could be in the lungs [10] or in the gingiva [11]. The inflammation of the joints is still the most prominent symptom and chronic joint inflammation resistant to medication is treated surgically. In this study we analyzed for the first time in detail the levels of protein bound citrulline and homocitrulline in several tissue samples of a single erosive arthritic surgery patient.
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