Journal of Translational Medicine | |
Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis | |
Juha Risteli3  Petri Lehenkari2  Eeva Alasaarela1  Jukka Melkko5  Marja-Kaisa Koivula3  Sanna Turunen4  | |
[1] Department of Internal Medicine, Division of Rheumatology, Oulu University Hospital, Oulu, Finland;Surgery Clinic, Oulu University Hospital, Oulu, Finland;Northern Finland Laboratory Centre NordLab, Oulu University Hospital, Oulu, Finland;Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland;Department of Pathology, Oulu University Hospital, Oulu, Finland | |
关键词: Carbamylation; Tissue; Autoantibodies; Rheumatoid arthritis; Homocitrulline; Citrulline; | |
Others : 826380 DOI : 10.1186/1479-5876-11-224 |
|
received in 2013-05-22, accepted in 2013-09-17, 发布年份 2013 | |
【 摘 要 】
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 ACPA-positive 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.
【 授权许可】
2013 Turunen et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140713094432240.pdf | 827KB | download | |
Figure 3. | 45KB | Image | download |
Figure 2. | 90KB | Image | download |
Figure 1. | 71KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Koivula MK, Heliovaara M, Ramberg J, Knekt P, Rissanen H, Palosuo T, Risteli J: Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis. Ann Rheum Dis 2007, 66:1450-1455.
- [2]Lundberg K, Nijenhuis S, Vossenaar ER, Palmblad K, van Venrooij WJ, Klareskog L, Zendman AJ, Harris HE: Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res Ther 2005, 7:R458-R467. BioMed Central Full Text
- [3]Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA: Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004, 50:380-386.
- [4]Suwannalai P, Trouw LA, Toes RE, Huizinga TW: Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis. Mod Rheumatol 2012, 22:15-20.
- [5]van de Stadt LA, de Koning MH, van de Stadt RJ, Wolbink G, Dijkmans BA, Hamann D, van Schaardenburg D: Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. Arthritis Rheum 2011, 63:3226-3233.
- [6]Lundberg K, Kinloch A, Fisher BA, Wegner N, Wait R, Charles P, Mikuls TR, Venables PJ: Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum 2008, 58:3009-3019.
- [7]Koivula MK, Aman S, Karjalainen A, Hakala M, Risteli J: Are there autoantibodies reacting against citrullinated peptides derived from type I and type II collagens in patients with rheumatoid arthritis? Ann Rheum Dis 2005, 64:1443-1450.
- [8]Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, Serre G: The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin. J Immunol 2001, 166:4177-4184.
- [9]Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GM, van Veelen PA, Levarht NE, van der Helm-van Mil AH, Cerami A, Huizinga TW, Toes RE, Trouw LA: Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci U S A 2011, 108:17372-17377.
- [10]Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, Ronnelid J, Harris HE, Ulfgren AK, Rantapaa-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L: A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006, 54:38-46.
- [11]Nesse W, Westra J, van der Wal JE, Abbas F, Nicholas AP, Vissink A, Brouwer E: The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation. J Clin Periodontol 2012, 39:599-607.
- [12]Turunen S, Koivula MK, Risteli L, Risteli J: Anticitrulline antibodies can be caused by homocitrulline-containing proteins in rabbits. Arthritis Rheum 2010, 62:3345-3352.
- [13]Koivula MK, Aman S, Alasaarela E, Karjalainen A, Hakala M, Risteli J: Inhibitory characteristics of citrullinated telopeptides of type I and II collagens for autoantibody binding in patients with rheumatoid arthritis. Rheumatology (Oxford) 2006, 45:1364-1369.
- [14]Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, Jakobsson PJ, Baum W, Nimmerjahn F, Szarka E, Sarmay G, Krumbholz G, Neumann E, Toes R, Scherer HU, Catrina AI, Klareskog L, Jurdic P, Schett G: Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 2012, 122:1791-1802.
- [15]Foulquier C, Sebbag M, Clavel C, Chapuy-Regaud S, Al Badine R, Mechin MC, Vincent C, Nachat R, Yamada M, Takahara H, Simon M, Guerrin M, Serre G: Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum 2007, 56:3541-3553.
- [16]Chang X, Yamada R, Suzuki A, Sawada T, Yoshino S, Tokuhiro S, Yamamoto K: Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis. Rheumatology (Oxford) 2005, 44:40-50.
- [17]Kleyer A, Finzel S, Rech J, Manger B, Krieter M, Faustini F, Araujo E, Hueber AJ, Harre U, Engelke K, Schett G: Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis 2013. Published online first, doi:10.1136/annrheumdis-2012-202958
- [18]Wang Z, Nicholls SJ, Rodriguez ER, Kummu O, Horkko S, Barnard J, Reynolds WF, Topol EJ, DiDonato JA, Hazen SL: Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nat Med 2007, 13:1176-1184.
- [19]Jaisson S, Gillery P: Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. Clin Chem 2010, 56:1401-1412.
- [20]Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, Knight JS, Friday S, Li S, Patel RM, Subramanian V, Thompson P, Chen P, Fox DA, Pennathur S, Kaplan MJ: NETs Are a Source of Citrullinated Autoantigens and Stimulate Inflammatory Responses in Rheumatoid Arthritis. Sci Transl Med 2013, 5:178ra40.