P154 Local low dose radiation induces systemic immune alterations in two experimental models of inflammatory arthritis. (March 2019)

• Record Type: Journal Article
• Authors: Deloch, L; Rückert, M; Seeling, M; Nimmerjahn, F; Fietkau, R; Frey, B; Gaipl, US
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 1
• Page Start: A67
• Page End: A67
• Publication Date: 2019-03
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2019.136
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Career situation of first and presenting author: Post-doctoral fellow. Introduction: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory autoimmune disease that mainly affects the joints with its hallmarks being synovial inflammation followed by cartilage and bone destruction. There are a plethora of treatment options available, however, not all patients respond properly. In these patients it is crucial to slow down bone loss and inflammation in a timely manner to prevent further damage. Here, a therapy with low-dose ionizing radiation, the so called low-dose radiotherapy (LD-RT), could be an additional option. Detailed knowledge on the underlying mechanisms of reduced bone destruction and immune-mediated pain levels in patients following LD-RT is still scarce. We already showed that LD-RT locally slows down disease progression in human TNFα transgenic (h TNFα tg) animals by mainly having an impact on bone metabolism. Objectives: We now aim to take a closer look on systemic immune-mediated effects of LD-RT in both, h TNFα tg mice, as a cytokine mediated model, and in the KRN serum transfer model, as an example for arthritogenic antibody dependence. Methods: h TNFα tg or serum-injected C57Bl/6 mice were locally irradiated with a single dose per fraction of 0.5Gy. After an observation period of 7 days (serum-injected mice) or 30 days (h TNFα -tg mice), blood, bone marrow as well as hind paws and synovial fluid was taken and analyzed using multicolor flow cytometry or histomorphometry. Results: Treatment of hind paws of serum-injected C57Bl/6 mice with 1 × 0.5 Gy resulted in a systemic immune modulation. In the peripheral blood, an increase of eosinophils and a decrease of B cells and NK cells were observed. In the bone marrow, the prominent alteration was a shift from CD8+ to CD4+ T cells in both, the irradiated and non-irradiated leg. Furthermore, dendritic cells were decreased. In h TNFα tg animals, inflammation was modulated in a systemic manner after local LD-RT, while bone protection was a local effect. Conclusions: We conclude that LD-RT is not only a valuable tool for locally reducing inflammation and bone loss in the affected joints, but also has beneficial systemic immune-mediated effects. The observed immune modulations in the peripheral blood were similar to those observed for patients treated with LD-RT within the observational IMMO-LDRT01 study (NCT02653079 ). In the future, placebo-controlled studies with high patient numbers are desirable to clinically prove LD-RT as therapy for RA. Acknowledgements: Supported by the German Federal Ministry of Education and Research (GREWIS, 02NUK017G and GREWIS-alpha, 02NUK050E). Disclosure of Interest: None declared.