AB0111 THE ROLE OF KLOTHO IN RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a chronic systemic and disabling disease affecting 0.5–1% of the general population. It is characterized by the presence of autoantibodies including rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). Klotho is a membrane-bound protein predominantly expressed in the kidney, parathyroid gland and choroid plexus that displays enzymatic and co-receptor functions, being involved in the prevention of aging, in the calcium-phosphate balance and in the reparative and fibrotic processes. klotho seems to play an essential role in the maintenance of vessel tone control, in tissue regeneration and reparation and in the electrolytic balance. Objectives: We aimed to compare serum Klotho levels between RA patients and healthy controls and the possible association between soluble Klotho with different characteristic of the disease. Methods: This cross-sectional study was performed in Vega-Baja Hospital, Orihuela (Spain) from November 2016 to May 2018. We prospectively enrolled 63 consecutive women patients affected by RA and followed at the Vega-Baja Hospital (Orihuela, Spain) and 65 matched healthy women controls. All patients included in this study had normal serum creatinine (Cr) levels and met the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA. ACPAs were detected using a second-generation ELISA (ACPAs) kit (ORGENTEC Diagnostika GmbH. Mainz, Germany) while IgM RF was determined as part of routine analysis by turbidimetric assay (Siemmens Healthcare Diagnostic Inc. NY, USA) according to the manufacturers’ instructions. Serum Klotho was analyzed using ELISA. Results: The mean serum total ACPAs and RF were 571.22±1040.89 U/ml and 173.73±751.8 U/ml, respectively. Serum Klotho concentrations were significantly higher in the RA patients than those in the control group: [4.68 (1.4-7.8) vs. 3.5 (0.6-6.1), ng/mL; P<0.0001]. They were positively associated with the presence of ACPA and RF (p<0.05). Klotho serum levels were higher in RA patients treated with biologic agents than in those undergoing conventional therapy (p =0.008). Conclusion: The increased serum klotho levels in RA patients, especially in those undergoing biologic therapy, may indicate a potential implication in the pathogenesis of the disease. References [1] Kozera L, Andrews J, Morgan AW. Cardiovascular risk and rheumatoid arthritis—the next step: differentiating true soluble biomarkers of cardiovascular risk from surrogate measures of inflammation. Rheumatology. 2011; 50: 1944-1954. [2] Hu MC, Shi M, Cho HJ, Adams-Huet B, Paek J, Hill K, et al. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol. 2015; 26(6):1290–1302. [3] Mazzotta C, Manetti M, Rosa I, et al. Proangiogenic effects of soluble -klotho on systemic sclerosis dermal microvascular endothelial cells. Arthritis Research & Therapy. 2017; 19(1): 27. Disclosure of Interests: Antonio Alvarez de Cienfuegos : None declared, Lucia Cantero-Nieto: None declared, José Alberto García-Gómez: None declared, Gema Robledo: None declared, Daniel Sánchez-Cano: None declared, Javier Martin Ibanez: None declared, Miguel A González-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Norberto Ortego: None declared