Serum RANKL Levels, Associate with Anti Citrullinated Proteins Antibodies (ACPA) in Early-Untreated Rheumatoid Arthritis and Is Modulated Following Methotrexate

Aase Haj Hensvold¹, Vijay Joshua¹, K. Lundberg², Nadine A. Defranoux³, Saedis Saevarsdottir⁴ and Anca I Catrina², ¹Rheumatology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden, Stockholm, Sweden, ²Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, ³Crescendo Bioscience Inc., South San Francisco, CA, ⁴Department of Medicine, Rheumatology Unit, The Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: bone biology and rheumatoid arthritis (RA), RANK/RANKL pathway

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

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).

Conclusion:

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.

Disclosure: A. H. Hensvold, None; V. Joshua, None; K. Lundberg, None; N. A. Defranoux, employment, 3; S. Saevarsdottir, None; A. I. Catrina, None.

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 .

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