Cytokine targets in lupus nephritis: Current and future prospects

Clin Immunol. 2019 Sep:206:42-52. doi: 10.1016/j.clim.2018.08.013. Epub 2018 Sep 2.

Abstract

Despite advancements in the care of lupus nephritis, a considerable proportion of patients may respond poorly or flare while on conventional immunosuppressive agents. Studies in murine and human lupus have illustrated a pathogenic role for several cytokines by enhancing T- and B-cell activation, autoantibodies production and affecting the function of kidney resident cells, therefore supporting their potential therapeutic targeting. To this end, there is limited post-hoc randomized evidence to suggest beneficial effect of belimumab, administered on top of standard-of-care, during maintenance therapy in lupus nephritis. Type I interferon receptor blockade has yielded promising results in preliminary SLE trials yet data on renal activity are unavailable. Conversely, targeting interleukin-6 and interferon-γ both failed to demonstrate a significant renal effect. For several other targets, preclinical data are encouraging but will require confirmation. We envision that high-throughput technologies will enable accurate patient stratification, thus offering the opportunity for personalized implementation of cytokine-targeting therapies.

Keywords: Autoantibodies; Autoimmune diseases; Biologics; Kidney; Lymphocytes; Personalized medicine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / antagonists & inhibitors*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Immunosuppressive Agents