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      Anti-citrullinated protein antibodies are linked to erosive disease in an observational study of patients with psoriatic arthritis

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          Abstract

          Objective. ACPAs are associated with bone destruction in RA. The aim of this study was to evaluate the association between ACPA and bone destruction in patients with a distinct inflammatory disorder, PsA.

          Methods. We used baseline data from a large observational study of PsA patients preparing to initiate treatment with adalimumab to analyse demographic and disease characteristics by ACPA status. To ensure a homogeneous PsA study population, only patients with active psoriatic skin manifestations who met Classification of Psoriatic Arthritis criteria for PsA were included in the analyses, thereby minimizing the risk of including misdiagnosed RA patients. Multiple logistic regression analyses were used to explore potential associations between ACPA seropositivity and bone destruction.

          Results. Of 1996 PsA patients who met the strict inclusion criteria, 105 (5.3%) were positive for ACPA. ACPA-positive patients had significantly higher swollen joint counts and 28-joint DAS values than ACPA-negative patients and significantly higher rates of erosive changes and dactylitis. Multiple logistic regression analysis confirmed the association of ACPA seropositivity with a 2.8-fold increase in the risk of erosive disease.

          Conclusion. As has been previously shown for RA, ACPA is associated with bone destruction in PsA, suggesting that the osteocatabolic effect of ACPA is not confined to RA but is also detectable in the different pathogenetic context of a distinct disease entity.

          Trial registration: ClinicalTrials.gov, NCT01111240

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          Most cited references15

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          Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin.

          Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and bone-resorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.
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            Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies.

            Anticitrullinated protein antibodies (ACPA) are a major risk factor for bone loss in rheumatoid arthritis (RA). We have recently shown that ACPA directly induce bone loss by stimulating osteoclast differentiation. As ACPA precede the clinical onset of RA by years, we hypothesised that ACPA positive healthy individuals may already show skeletal changes.
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              Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA.

              To determine whether there is an additive effect of anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of bone erosions in patients with rheumatoid arthritis (RA) METHODS: 242 patients with RA received high-resolution peripheral quantitative CT (HR-pQCT) scans of the metacarpophalangeal joints. Demographic and disease-specific parameters including ACPA and RF levels were recorded from all patients. Erosion numbers and their size were assessed in 238 patients at 714 individual joints (MCP 2, 3 and 4) and 5712 sites (each 4 quadrants in metacarpal heads and phalangeal bases). The volume of erosions was calculated by a semiellipsoid formula.
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                Author and article information

                Journal
                Rheumatology (Oxford)
                Rheumatology (Oxford)
                brheum
                rheumatology
                Rheumatology (Oxford, England)
                Oxford University Press
                1462-0324
                1462-0332
                October 2016
                21 June 2016
                21 June 2016
                : 55
                : 10
                : 1791-1795
                Affiliations
                1Division of Rheumatology, University Hospital Frankfurt, Goethe University
                2Project Group Translational Medicine & Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Frankfurt am Main
                3Comprehensive Center of Inflammation Medicine, University Hospital Schleswig-Holstein Campus, Lübeck
                4GKM Gesellschaft für Therapieforschung mbH, München
                5AbbVie Deutschland GmbH & Co KG, Wiesbaden, Germany
                Author notes
                Correspondence to: Harald Burkhardt, Division of Rheumatology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D 60590 Frankfurt/Main, Germany. E-mail: harald.burkhardt@ 123456kgu.de
                Article
                kew229
                10.1093/rheumatology/kew229
                5034218
                27330166
                630870d1-a6b8-4c93-93bd-d299034ae49c
                © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 24 August 2015
                : 22 April 2016
                Page count
                Pages: 5
                Categories
                Clinical Science
                263

                Rheumatology
                adalimumab,anti-citrullinated protein antibodies,psoriatic arthritis,osteoporosis,erosions,observational study

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