OP0326 ACPA-INDUCED PAIN-BEHAVIOR, BONE LOSS AND TENDON INFLAMMATION IN MICE: A NOVEL MODEL FOR THE PRE-DISEASE PHASES OF ACPA-POSITIVE RHEUMATOID ARTHRITIS

Background: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPAs) are associated with bone loss and pain. Recently, tenosynovitis has been suggested as a predicting factor for arthritis progression in individuals at-risk for RA. Objectives: We aimed to investigate if transfer of human ACPAs into mice could induce tenosynovitis and/or subclinical inflammation. Methods: Monoclonal ACPA (1325:04C03 and 1325:01B09) and control (1362:01E02) antibodies (mAbs) were generated from synovial plasma or memory B cells of RA patients. 2mg of combination of monoclonal ACPAs or control antibody were injected in BALB/c female mice (age 12-16 weeks) (n= 9). Pain-like behavior was monitored by measuring mechanical hypersensitivity using von Frey filaments every 3 days and estimation by up-down Dixon method. Bone morphometrics was analyzed by micro-CT. Using specially designed mobilization casts, dedicated mouse MRI coils, and gadolinium enhanced contrast medium, the hind limbs of these mice were scanned in a 9.4 T scanner and resulting T1-weighted images were evaluated for signs of soft tissue joint inflammation. The MRI images were scored for the presence of joint involvement and tendon inflammatory changes by 3 readers in a blinded manner. Results: ACPAs (1325:04C03 and 1325:01B09) induced pain-like behavior (lasting for at least 4 weeks) and reduction of the trabecular and cortical bone thickness in the hind limbs as compared to control monoclonal antibodies (p Conclusion: We show that ACPA induces pain-like behavior, bone loss and tendon sheath inflammation in mice, a model that mimics the preclinical state of ACPA positive RA. References: [1]Harre, U. et al. J Clin Invest (2012) [2]Krishnamurthy, A. et al. Ann Rheum Dis (2016, 2019), JI 2019 [3]Wigerblad, G. et al. Ann Rheum Dis (2016, 2019) [4]KleyerA, Seminars in Arthritis and Rheumatism (2016) Disclosure of Interests: Akilan Krishnamurthy: None declared, Yogan Kisten: None declared, Alexandra Circiumaru: None declared, Koji Sakurabas: None declared, Patrik Jarvolli: None declared, Juan Jimenez Jimenez Andrade: None declared, Peter Damberg: None declared, Heidi Wahamaa: None declared, Vivianne Malmstrom Grant/research support from: VM has had research grants from Janssen Pharmaceutica, Lars Klareskog: None declared, Camilla Svensson: None declared, Bence Rethi: None declared, Anca Catrina: None declared