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CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease

Author

Listed:
  • Sheila K. Pierson

    (University of Pennsylvania)

  • Laura Katz

    (Medidata Solutions)

  • Reece Williams

    (University of Pennsylvania)

  • Melanie Mumau

    (University of Pennsylvania)

  • Michael Gonzalez

    (University of Pennsylvania)

  • Stacy Guzman

    (University of Pennsylvania)

  • Ayelet Rubenstein

    (University of Pennsylvania)

  • Ana B. Oromendia

    (Medidata Solutions)

  • Philip Beineke

    (Medidata Solutions)

  • Alexander Fosså

    (Oslo University Hospital
    University of Oslo, Oslo, Norway; Oslo University Hospital)

  • Frits van Rhee

    (University of Arkansas for Medical Sciences)

  • David C. Fajgenbaum

    (University of Pennsylvania)

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.

Suggested Citation

  • Sheila K. Pierson & Laura Katz & Reece Williams & Melanie Mumau & Michael Gonzalez & Stacy Guzman & Ayelet Rubenstein & Ana B. Oromendia & Philip Beineke & Alexander Fosså & Frits van Rhee & David C. , 2022. "CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34873-7
    DOI: 10.1038/s41467-022-34873-7
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    Cited by:

    1. Takuya Harada & Yoshikane Kikushige & Toshihiro Miyamoto & Kazuko Uno & Hiroaki Niiro & Atsushi Kawakami & Tomohiro Koga & Koichi Akashi & Kazuyuki Yoshizaki, 2023. "Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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