HM71224, a selective Bruton’s tyrosine kinase inhibitor, attenuates the development of murine lupus

• DOI: 10.1186/s13075-017-1402-1
• Publication Date: 2017-09-26T11:27:20Z
• Authors: Yu-Yon Kim; Ki Tae Park; Sun Young Jang; Kyu Hang Lee; Joo-Yun Byun; Kwee Hyun Suh; Young-Mi Lee; Young Hoon Kim; Kwang Woo Hwang
• Keywords: Blood urea nitrogen

Systemic lupus erythematosus (SLE) is associated with B cell hyperactivity, and nephritis (LN), in particular, promoted by the production of autoantibodies immune complex deposition. Bruton's tyrosine kinase (BTK) plays critical roles receptor-related Fc signaling. We aimed to investigate impact therapeutic intervention HM71224 (LY3337641), a selective BTK inhibitor, on development murine SLE-like disease features.We examined effects features MRL/lpr NZB/W F1 mice. The disease-related skin lesion was macroscopically observed mice, splenomegaly lymphadenopathy determined weight spleen cervical lymph node. renal function evaluated measuring blood urea nitrogen, serum creatinine, urine protein, damage assessed histopathological grading. Survival rate during administration period. inhibition investigated splenocytes from both mice using flow cytometry. Autoantibody measured ELISA.HM71224 effectively suppressed splenic B220+GL7+, B220+CD138+, B220+CD69+ counts, anti-dsDNA IgG reduced node enlargement. compound also prevented lesions caused development, ameliorated inflammation increased nitrogen decreased proteinuria. Furthermore, mortality mouse models.Our results indicate that hyperactivity significantly attenuated SLE LN rodent models.