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Connective tissue diseases

Is APRIL fooling us all in SLE?

Nature Reviews Rheumatology volume 8, page 63 (2012)Cite this article

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In 2011, belimumab, an anti-BAFF antibody, was approved for the treatment of systemic lupus erythematosus (SLE). APRIL, a cytokine closely related to BAFF, is also a potential therapeutic target in SLE. However, “direct evidence either in support of or against a role for APRIL per se in SLE had never been reported,” says William Stohl, of the University of Southern California, Los Angeles. Now, Stohl and collaborators have presented data that increase our knowledge of APRIL's influence on SLE pathogenesis.

In contrast to Stohl and co-workers' previous findings in Baff−/− mice, their new data reveal that APRIL deficiency in SLE-prone NZM 2328 mice offers no protection against, and might even slightly exacerbate, development of the disease. The authors speculate that any worsening of disease might be explained by decreased heterotrimerization of BAFF and APRIL in April−/− mice, which could promote formation of more potently signal-promoting BAFF homotrimers. “We can use APRIL-deficient mice as a starting point to elucidate the critical BAFF–BAFF receptor interactions in SLE without any potentially confounding effects from APRIL,” suggests Stohl. “This could ultimately lead to more selective therapeutic targeting within the greater 'BAFF axis' and greater therapeutic benefit,” he continues.

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ORIGINAL RESEARCH PAPER

  1. Jacob, C. O. et al. Dispensability of APRIL to development of systemic lupus erythematosus in NZM 2328 mice. Arthritis Rheum. doi:10.1002/art.33458.

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  1. David Killock
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Killock, D. Is APRIL fooling us all in SLE?. Nat Rev Rheumatol 8, 63 (2012). https://doi.org/10.1038/nrrheum.2011.209

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