CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease

11/24/2022 In a study published in the journal Nature Communications, researchers at the CDCN discovered that an inflammatory protein called CXCL13 can be measured in iMCD patients shortly after receiving siltuximab to help predict whether it will work or not. This allows doctors to determine whether they should add additional treatments or not and could help to save lives. This also has implications for related diseases like COVID where biomarkers like this could be used to guide therapy.


Idiopathic multicentric Castleman disease (iMCD) is a rare and poorlyunderstood 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, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N=42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate diseasemediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD.

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