Research ArticleAutoimmunity

A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity

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Science Translational Medicine  24 Apr 2019:
Vol. 11, Issue 489, eaar6584
DOI: 10.1126/scitranslmed.aar6584

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Curbing CD40 signaling

The CD40 axis is a major collaborative mechanism of B and T cell responses. Previous attempts to disrupt this pathway to treat autoimmune disease led to adverse thrombotic events due to engagement of Fc receptors and platelet expression of CD40 ligand (CD40L). To avoid this issue, Karnell et al. designed a nonantibody scaffold protein, VIB4920, which blocks human CD40L. VIB4920 inhibits B cell activation but does not induce platelet aggregation in vitro. VIB4920 administration resulted in blunted responses to immunization in healthy people, and people with rheumatoid arthritis experienced reduced disease activity. No thrombotic side effects were encountered in either clinical trial. This next-generation therapeutic has the potential to be widely used to treat various autoimmune diseases.