BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus

• DOI: 10.1038/s41467-018-03620-2
• Publication Date: 2018-04-04T02:49:52Z
• Authors: Woori Shin; Hyun Tae Lee; Heejin Lim; Sang Hyung Lee; Ji Young Son; Jee Un Lee; Ki-Young Yoo; Seong Eon Ryu; Jaejun Rhie; Ju Yeon Lee; Yong-Seok Heo
• Keywords: Belimumab

BAFF, a member of the TNF superfamily, has been recognized as good target for autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by FDA use in treating systemic lupus erythematosus. However, molecular basis BAFF neutralization belimumab remains unclear. Here our crystal structure BAFF-belimumab Fab complex shows precise epitope and BAFF-neutralizing mechanism belimumab, demonstrates that therapeutic activity involves not only antagonizing BAFF-receptor interaction, but also disrupting formation more active 60-mer to favor induction less trimer through interaction with flap region BAFF. In addition, HCDR3 loop mimics DxL(V/L) motif receptors, thereby binding similar manner endogenous receptors. Our data thus provides insights design new drugs targeting treatment