Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems. Autoantibodies, which are produced by B cells, contribute to development of SLE. Recent studies have also shown that type 1 interferons (IFNs) and associated inflammatory molecules are highly expressed in serum from SLE patients. Specialized cells called plasmacytoid dendritic cells (pDCs) primarily produce type 1 IFNs and may represent a therapeutic target for SLE therapies. In this issue of JCI Insight, research groups led by Ian Wicks of the University of Melbourne and Nicholas Wilson of CSL Limited developed an antibody (CSL362) directed against the surface molecule CD123 that targets and depletes pDCs and other cells implicated in SLE. CD123 was found on the surface of pDCs and basophils in blood from both healthy volunteers and SLE patients. CSL362 depleted these populations in whole blood and reduced production of type 1 IFN and type 1 IFN-induced genes, while also preventing expansion of antibody-producing cells. Importantly, this antibody effectively depleted pDCs and basophils in non-human primates and reduced induction of type 1 IFN-associated genes in the peripheral blood cells of these animals. Further studies will be required to determine if this antibody will benefit patients with SLE.
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TITLE: A cytotoxic anti-IL3Rα antibody targets key cells and cytokines implicated in systemic lupus erythematosus
AUTHOR CONTACT:
Ian Wicks
Walter & Eliza Hall Institute of Medical Research
Email: wicks@wehi.edu.au
Nicholas Wilson
CSL Limited
Email: nick.wilson@csl.com.au
View this article at: http://insight.jci.org/articles/view/86131?key=b63987c3923fdc4341f4
JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to http://www.insight.jci.org.
Journal
JCI Insight