Cytokine and chemokine multiplex analysis-based exploration for potential treatment and prognostic prediction in large-vessel vasculitis: A preliminary observational study

Nobuya Abe, Michihiro Kono, Michihito Kono, Takayuki Katsuyama, Kazumasa Ohmura, Taiki Sato, Kohei Karino, Yuichiro Fujieda, Masaru Kato, Rie Hasebe, Masaaki Murakami, Tatsuya Atsumi

Research output: Contribution to journalArticlepeer-review

Abstract

Large-vessel vasculitis (LVV) is subclassified into two phenotypes; Takayasu arteritis and giant cell arteritis. Although the pathogenesis of LVV is not fully established, IL-6−IL-17 axis and IL-12−IFN-γ axis play critical roles in the disease development. We aimed to clarify the association between the disease state and cytokine/chemokine levels, to assess disease course as prognosis and to predict regulators in patients with LVV using the blood profiles of multiple cytokines/chemokines. This retrospective analysis comprised 35 LVV patients whose blood were collected, and multiplex cytokine/chemokine analysis with 28 analytes was performed. The differences of cytokines/chemokines corresponding disease status, upstream regulator analysis, pathway analysis and cluster analysis were conducted using the cytokines/chemokines profile. Relapse-free survival rate was calculated with Kaplan-Meier analysis in the classified clusters. In the robust analysis, IL-4, CCL2/MCP-1, TNFSF13/APRIL, TNFSF13B/BAFF, CHI3L1 and VEGF-A levels were significantly changed after treatment. Untreated LVV patients demonstrated activation of NFκB-related molecules and these patients are potentially treated with JAK/STAT inhibitors, anti-TNF-α inhibitors and IL-6 inhibitors. Cluster analysis in active LVV patients revealed two clusters including one with high blood levels of IL-1β, IL-6, IL-17, IL-23 and CCL20/MIP-3. A subgroup of the LVV patients showed activated IL-17 signature with high relapse frequency, and JAK/TyK2 inhibitors and IFN-γ inhibitors were detected as potentially upstream inhibitors. Blood cytokine/chemokine profiles would be useful for prediction of relapse and potentially contributes to establish therapeutic strategy as precision medicine in LVV patients.

Original languageEnglish
Article number1066916
JournalFrontiers in immunology
Volume13
DOIs
Publication statusPublished - Nov 23 2022

Keywords

  • chemokine
  • clustering
  • cytokine
  • giant cell arteritis
  • Janus-kinase inhibitor
  • large vessel vasculitis
  • proteomics
  • Takayasu arteritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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