AB0120 THE EFFECT OF INFLAMMATORY SERA FROM DIFFERENT FORMS OF AXIAL SPONDYLOARTHRITIS ON THE OSTEOCLASTOGENIC POTENTIAL OF MONONUCLEAR PRECURSORS IN BLOOD
Authors: P. Dankova, E. Sebova, P. Škubica, J. Horinkova, M. Gregová, K. Pavelka, M. Husakova
Journal: Annals of the Rheumatic Diseases (2020)

Background: Spondyloarthritis (SpA) is characterized by pathological bone resorption and higher risk of osteoporosis. Inflammation accompanying the disease may activate mononuclear precursors in blood that are able to differentiate into osteoclasts, bone resorbing cells [1,2] , and thus substantially contribute to bone resorption and aggravation of symptoms characteristic for this chronic disease. Objectives: The aim of this pilot study is i) to figure out whether the inflammatory factors present in blood sera of SpA patients activate the osteoclastogenic potential of peripheral blood monocytes (PBM) derived from healthy subjects; ii) to find out whether this effect differs among sera from three forms of SpA, short-term non-radiographic (nr-axSpA) and radiographic (r-axSpA) SpA, and long-term ankylosing spondyloarthritis (AS), and finally iii) to assess whether the stimulatory effect of serum from SpA patients on osteoclastogenesis of healthy PBM reflects the altered clinical markers of inflammation and bone metabolism. Methods: To simulate inflammatory condition characteristic for nr-axSpA, r-axSpA or AS, we created pool of 10 AS sera together with age- and sex-matched pools of nr-axSpA, r-axSpA and AxC (sera from healthy subjects). Disease duration of nr-axSpA and r-axSpA was set up to less than 2 years. The ASDAS score of AS form was significantly higher compared to the score of short-term forms of disease (P &lt; 0.05). PBM from 6 healthy donors were cultured for 14 days in DMEM supplemented with 25 ng/ml macrophage colony-stimulating factor (M-CSF), 0.5 ng/ml receptor-activator of nuclear factor kappa B ligand (RANKL) and in parallel with 10% pooled human sera nr-axSpA, r-axSpA, AS and AxC. TRAP positive cells with 3 or more nuclei were recognized as osteoclasts and counted. Results: Cultivation of PBM in the presence of both, diseased and healthy human sera increases number of osteoclasts in comparison to cultures without human sera. The strongest osteoclastogenic capacity develop PBM affected by pooled AS sera (2.9 times increase in osteoclast number compared to culture without human sera, P &lt; 0.05), the lowest osteoclastogenic potential was detected in culture with pooled sera from healthy donors (2.1 times, P = NS). Pooled nr-axSpA, r-axSpA and AS sera do not appear to differ significantly among each other in size of their effect on PBM; nevertheless, trend to lowest numbers of osteoclasts can be seen in culture with r-axSpA sera (P = NS). Conclusion: Cytokine milieu in human sera seems to have a pro-osteoclatogenic effect regardless of its origin with respect to healthy condition. However, inflammatory factors present in the sera of SpA patients enhance the osteoclastogenic potential of PBM, as documented especially in AS sera presenting with significant, 7fold increased serum CRP levels (P = 0.003), and thus may contribute to aggravation of the osteoporotic condition of SpA patients. References: [1]Amarasekara, DS, Yu, J, Rho, J (2015). Bone loss triggered by the cytokine network in inflammatory autoimmune diseases. J Immune Res. 2015:832127 [2]Amarasekara, D S, Yun H, Kim S, Lee N, Kim H, Rho J (2018). Regulation of Osteoclast Differentiation by Cytokine Networks. Immune Netw. Feb 7;18(1):e8 Acknowledgments: Project MH CR 00023728 and MEYS CR Progres Q43 Disclosure of Interests: Pavlina Dankova: None declared, Eva Sebova: None declared, Patrik Škubica: None declared, Jana Horinkova: None declared, Monika Gregová Consultant of: Novartis, Abbvie, Paid instructor for: Novartis, Speakers bureau: Novartis, Abbvie, MSD, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Marketa Husakova Speakers bureau: Novartis