Analysis of the mechanisms of intravenous immunoglobulin-resistant Kawasaki disease using iPS cell technology

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Ikeda Kazuyuki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30507786)
• Co-Investigator(Kenkyū-buntansha): HAMAOKA Kenji 京都府立医科大学, 大学院医学研究科, 教授 (60189602) ; OSAFUNE Kenji 京都大学, iPS細胞研究所, 教授 (80502947)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 川崎病 / iPS細胞 / IVIG不応

Outline of Final Research Achievements

Objective: This study clarifies the mechanisms of IVIG resistance in Kawasaki disease (KD) using an iPSC disease model.
Methods and Results:Dermal fibroblasts or PBMNCs from two IVIG-resistant and two IVIG-responsive KD patients were reprogrammed by the episomal vector-mediated transduction of reprogramming factors. KD patient-derived iPSCs were differentiated into ECs (iPSC-ECs). The gene expression profiles of iPSC-ECs generated from IVIG-resistant and IVIG-responsive KD patients were compared by RNA-sequencing analyses. We found that the expression of chemokine X was significantly up-regulated in iPSC-ECs from IVIG-resistant KD patients. Additionally, GSEA revealed that gene sets involved in IL-6 signaling were also up-regulated.
Conclusions:Our mechanistic analyses suggest that chemokine X, which plays a role in leukocyte transmigration, is a candidate key molecule for IVIG resistance. They also indicate that up-regulation of IL-6 related genes may be involved in this pathogenesis.

Free Research Field

小児循環器・川崎病