Early longitudinal proteomic changes during sirolimus therapy in tocilizumab-refractory idiopathic multicentric Castleman disease

Clicks: 1
ID: 325176
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal

Ranked #182 of 197 articles by views in Lara D. Veeken

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 197 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
OBJECTIVES: To characterise early treatment-associated changes in circulating immune mediators following sirolimus initiation in patients with tocilizumab-resistant idiopathic multicentric Castleman disease (iMCD). METHODS: As a predefined translational sub-analysis of a placebo-controlled exploratory trial, we performed longitudinal serum proteomic profiling using a RayBiotech L-1000 antibody array (∼1,000 proteins) in a sirolimus-treated patient with tocilizumab-resistant iMCD. Serum samples were obtained at baseline and at weeks 8, 12, and 16. Protein expression levels were normalised, log₂-transformed, and analysed for stepwise temporal changes. Pathway-level effects were assessed using gene set enrichment analysis (GSEA). RESULTS: Six immune mediators-CCR5, ICAM-1, RANTES, S100A8/A9, CD40 ligand, and OX40 ligand-showed consistent monotonic decreases from baseline through week 12. Heatmap visualisation of the top 80 dynamically regulated proteins confirmed a broader suppression of immune activation signatures. GSEA demonstrated significant negative enrichment of coagulation, complement, IFN-γ response, IL-6-JAK-STAT3 signalling, TNFα signalling via NF-κB, and MMP-driven extracellular matrix remodelling. Temporal analysis confirmed sustained downregulation of IFN-γ-inducible chemokines (CXCL9, CXCL10, CXCL11) and a broad panel of interferon-response mediators through weeks 12 and 16. CONCLUSIONS: Early and coordinated decreases in immune-inflammatory mediators were observed during sirolimus therapy in tocilizumab-resistant iMCD, extending beyond the IL-6 axis to encompass IFN-γ, TNF-α, and chemokine signalling. These findings are hypothesis-generating and provide a mechanistic rationale for mTOR inhibition as a potential disease-modifying strategy warranting evaluation in future controlled studies.
Reference Key
openalex_W7203599404 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Tomohiro Koga, Shoichi Fukui, Remi Sumiyoshi, Toshimasa Shimizu, Naoki Hosogaya, Chizu Fukushima, Hiroshi Yamamoto, Hajime Yoshifuji, Shinji Higa, Atsushi Kawakami
Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag426
URL
https://doi.org/10.1093/rheumatology/keag426
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.