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  • Title: CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease.
    Author: Pierson SK, Katz L, Williams R, Mumau M, Gonzalez M, Guzman S, Rubenstein A, Oromendia AB, Beineke P, Fosså A, van Rhee F, Fajgenbaum DC.
    Journal: Nat Commun; 2022 Nov 24; 13(1):7236. PubMed ID: 36433996.
    Abstract:
    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, 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 disease mediators 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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