CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease
Authors/Creators
- 1. University of Pennsylvania
- 2. Medidata Solutions
- 3. Oslo University Hospital, University of Oslo
- 4. University of Arkansas for Medical Sciences
Description
Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients. Patients not responding to siltuximab often require immediate therapeutic changes to avert life-threatening multi-organ failure, but no biomarkers exist to provide an early indication after treatment initiation whether siltuximab is likely to work. We analyzed 1,178 proteins in iMCD (N=88), healthy control (N=42), and related disease (N=60) patients’ sera to search for disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) was identified and validated as a top up-regulated protein in iMCD. CXCL13 also demonstrated early and significant decline in siltuximab responders compared to non-responders; a 17% reduction by day 8 following siltuximab initiation was predictive of response. Our discoveries suggest that CXCL13 is a predictive biomarker of response to siltuximab.
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