The role of adenosine receptor modulation in systemic lupus erythematosus disease progression 4029

Abstract Description Adenosine receptor dysregulation has been linked with lupus disease exacerbation as it plays a crucial role in immune modulation. We hypothesized that either activation of A2AR or inhibition of the A2BR would decrease lupus disease severity. Lupus prone NZB/W female mice were intraperitoneally injected daily for 12 weeks with ADO-5024 (A2BR antagonist) or ADO-6001 (A2AR agonist) beginning at 20 weeks-of-age. As controls, mice received dexamethasone (DEX) or PBS. As they aged, urine was assessed for proteinuria and inflammatory cytokines were measured in the sera. At 32 weeks-of-age, the mice were euthanized, and spleen and kidney tissue were assessed. Our findings showed that mice treated with the ADO-5024 had overall attenuated lupus disease not statistically different from DEX treatment, while those treated with the ADO-6001 and PBS were statistically different from the former across all parameters including proteinurea, renal pathology, and inflammatory cytokine expression. Mice treated with ADO-5024 showed decreased inflammatory profiles as observed by multiplex assay measuring cytokines like BAFF, TNF-a, and more. The ADO-5024 and DEX treated mice showed reduced IgG and C3 deposition and decreasing trends of glomerular and interstitial inflammation score compared to the PBS treated or ADO-6001 treated animals. Overall, our data suggests that inhibition of the A2BR may have therapeutic potential in treating lupus disease and more specifically lupus nephritis. Funding Sources Supported by Virginia Catalyst Grant; and NIH 1U2CDK129500-01 Topic Categories Basic Autoimmunity (BA)