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. 2024 Apr 15;15:1354969. doi: 10.3389/fimmu.2024.1354969

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Copyright © 2024 Hirahara, Kirino, Soejima, Iizuka, Yoshimi, Fujieda, Atsumi, Tono, Kobayashi, Meguro, Takeuchi, Sakamaki, Takeno, Mizuki and Nakajima

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Cluster analysis of cytokines combined with BDCAF and therapeutic agents, and exploration of expression variation cytokines. (A) Heatmap of consensus matrices of k=5 (left). The same patients are symmetrically placed in rows and columns. The right is a Cumulative Distribution Function (CDF) plot, where the x-axis is the consensus index, and the y-axis is the cumulative percentage of patients. (B) Summarized heatmap depicting serum cytokine concentrations and percentage of non-remission (BDCAF ≥ 1) and percentage of TNF inhibitor use for each cluster. Cytokines are expressed as a Z-score. (C) Kaplan–Meier curves for each cluster. (D) A Volcano plot illustrating the difference in cytokine expression between Cluster A and E. The vertical axis represents log10FDR, with the green line indicating an FDR of 0.05. (E) Kaplan–Meier curves for the first BDCAF survey data (n=251) stratified by serum IL-6 concentration. (F) pruned survival decision trees with the minimum cross-validation error constructed for the first survey data (n=251, left), and the second survey data (n=135, right). Disease activity, TNF inhibitors use, and serum IL-6 concentration was used as variable. In each node, color indicates relative hazard ratio (HR), with darker orange signifying higher and darker green suggesting lower. BDCAF, Behçet disease current activity form; TNF, Tumor necrosis factor; IL, Interleukin; IFN, Interferon; MCP, Macrophage chemotactic protein.