A novel IgG1 monoclonal antibody against xanthine oxidase alleviates inflammation induced by potassium oxonate in mice

作者:Liu, Xiaoran; Li, Ya; Li, Zhixin; Wei, Xiaomin; Ma, Yanjie; Cheng, Peng; Jiao, Rui; Fang, Jinzhi; Xing, Yun; Tang, Jiali; Wang, Min; Li, Taiming*
来源:International Journal of Biological Macromolecules, 2018, 112: 537-547.
DOI:10.1016/j.ijbiomac.2018.01.171

摘要

Xanthine oxidase (XOD) is a key enzyme that catalyzes xanthine to uric acid. Most of the urate-lowering medicines targeting XOD have a limited effect on alleviating inflammation in spite of significant effects on decreasing serum uric acid level. In this study, we produced and characterized a novel monoclonal antibody (Anti-XOD mAb) using hybridoma technology based on a novel peptide OI5P-1(O-IA2(5)-P2-1),which containing a B-cell epitope of XOD and a novel Th2 built-in adjuvant I5P-1(IA2(5)-P2-1). Results of western blotting and cross-reactivity assay indicated that the mAb binds specifically to XOD and the affinity was 2.523 x 10(10) L/mol. The mAb reduced serum uric acid level and hepatic xanthine oxidase activity in potassium oxonate induced mice. A decreased methane dicarboxylic aldehyde level and an improved superoxide dismutase level in mAb treated mice indicated anti-lipid peroxidation effects of the mAb. Moreover, the mAb showed a significant immunomodulatory effect which could shift Th1/Th2 balance to Th2-dominant immunity. The mAb treatment alleviates inflammation induced by potassium oxonate, superior to the small molecule allopurinol treatment. For the first time, these results showed that the anti-XOD mAb may serve as a promising therapeutic approach for inflammatory response related to uric acid.