Session Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Receptor Activator of Nuclear factor Kappa-b Ligand (RANKL) is a key regulator of bone metabolism. Anti-citrullinated (cit) protein antibodies (ACPA) have been suggested to cause bone destruction by osteoclast activation. We investigated the relationship between RANKL and ACPA in early-untreated rheumatoid arthritis (RA) patients.
Methods: Patients with newly diagnosed untreated RA (n=183) were analysed at baseline and 3 months after initiating methotrexate (MTX) treatment. Serum RANKL (total RANKL), ACPA (anti-CCP2) and ACPA specificities (anti cit-vimentin, anti cit-enolase and anti cit-fibrinogen) were determined by enzyme-linked immunosorbent assay (ELISA). Synovial RANKL expression was evaluated by immunohistochemistry in a subgroup of patients (N=15). The relationship between anti cit-vim antibodies and bone destruction was further validated in 1116 RA patients included in the EIRA cohort. Pearson’s Chi-Square test, Wilcoxon rank sum test, Wilcoxon signed rank test and linear regression models were used.
Results: Serum RANKL concentration was significantly higher (p <0.05) in ACPA-positive (median: 689 pmol/L, IQR 342-1253) compared with ACPA-negative (median: 159 pmol/L, IQR 96-243) patients and this difference was also seen for synovial RANKL expression. Serum RANKL associated with ACPA and bone erosions in rheumatoid factor (RF) negative patients (p <0.05). Among ACPA specificites, anti-cit-vim was associated with higher RANKL concentration and higher prevalence of bone erosion (p <0.05). Significant reductions in both serum RANKL and ACPA levels were observed after 3 months of MTX treatment (p <0.05).
RANKL was elevated in ACPA-positive and in anti cit-vimentin positive early untreated RA patients and associated with bone erosions. These findings give further support for an early direct pathogenic link between ACPA and bone destruction in RA.
To cite this abstract in AMA style:Hensvold AH, Joshua V, Lundberg K, Defranoux NA, Saevarsdottir S, Catrina AI. Serum RANKL Levels, Associate with Anti Citrullinated Proteins Antibodies (ACPA) in Early-Untreated Rheumatoid Arthritis and Is Modulated Following Methotrexate [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/serum-rankl-levels-associate-with-anti-citrullinated-proteins-antibodies-acpa-in-early-untreated-rheumatoid-arthritis-and-is-modulated-following-methotrexate/. Accessed December 4, 2021.
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