Therapeutic targeting of the BAFF/APRIL axis in systemic lupus erythematosus

Expert Opin Ther Targets. 2014 Apr;18(4):473-89. doi: 10.1517/14728222.2014.888415. Epub 2014 Feb 13.


Introduction: The B-cell activating factor (BAFF) axis comprises two ligands (BAFF and APRIL) and three receptors (BCMA, TACI, BR3). BAFF is a vital B-cell survival factor and overexpression of BAFF in both mice and humans is associated with systemic lupus erythematosus (SLE). The anti-BAFF monoclonal antibody (mAb), belimumab, was recently approved by the US FDA for the treatment of adult SLE patients, and three additional BAFF antagonists (atacicept, blisibimod, tabalumab) are presently being evaluated in SLE Phase-III trials.

Areas covered: The general biological properties of the individual elements of the BAFF/APRIL axis are reviewed, with emphasis placed on molecular interactions and the potential relevance of each individual element to SLE.

Expert opinion: The success of belimumab, an agent which promotes only modest B-cell depletion, is contrasted with the failure of the anti-CD20 mAb rituximab, an agent which promotes profound B-cell depletion, and multiple arguments are offered to explain this apparent paradox. Real and perceived limitations to belimumab therapy are presented, and possibilities for other therapeutic agents that target specific elements of the BAFF/APRIL axis are discussed.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • B-Cell Activating Factor / antagonists & inhibitors*
  • B-Cell Activating Factor / immunology
  • Drug Delivery Systems / methods*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / antagonists & inhibitors*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology


  • Antibodies, Monoclonal, Humanized
  • B-Cell Activating Factor
  • Immunosuppressive Agents
  • TNFSF13B protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • belimumab