Pathogenesis of IgG4-related disease-Molecular biological approaches

DOI
  • Tsuboi Hiroto
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Iizuka Mana
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Takahashi Hiroyuki
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Asashima Hiromitsu
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Hirota Tomoya
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Kondo Yuya
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Nakai Yuji
    Functional Food Science and Nutrigenomics, Graduate School of Agricultural and Life Sciences, The University of Tokyo Institute for Food Sciences, Hirosaki University
  • Abe Keiko
    Functional Food Science and Nutrigenomics, Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • Tanaka Akihiko
    Faculty of Dental Science, Kyushu University
  • Moriyama Masafumi
    Faculty of Dental Science, Kyushu University
  • Nakamura Seiji
    Faculty of Dental Science, Kyushu University
  • Yoshihara Toshio
    Department of Otorhinolaryngology, Tokyo Women's Medical University
  • Matsumoto Isao
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
  • Sumida Takayuki
    Department of Internal Medicine, Faculty of Medicine, University of Tsukuba

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Other Title
  • IgG4関連疾患の病因―分子生物学的アプローチ―

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Abstract

<p><Objective> To compare gene expression in IgG4-related disease (IgG4-RD) with Sjögren’s syndrome (SS) comprehensively, and to identify disease-related molecules.<br><Methods> Gene expression was analyzed by DNA microarray in labial salivary gland (LSG) of IgG4-RD (n=5), SS (n=5), and healthy controls (HC) (n=3). Gene expression patterns were compared by principal component analysis (PCA), and differentially expressed genes (DEGs) between IgG4-RD and SS were identified in pairwise comparisons. Validation of the result was performed by quantitative PCR and immunofluorescence (IF) staining for highly expressed DEGs in IgG4-RD than in SS.<br><Results> Gene expression patterns in IgG4-RD, SS, and HC were quite different with each other in PCA. In IgG4-RD, 1321 up-regulated and 1320 down-regulated genes compared with SS were identified as DEGs. Quantitative PCR validated significantly higher expression of chemokine (C-C motif) ligand 18 (CCL18) which has chemotactic activity on various lymphocytes and induces collagen production from fibroblasts, and lactotransferrin (LTF) which is an abundant iron-binding protein in milk and has the wide range of functions such as the maturation of dendritic cells (DCs), in LSG of IgG4-RD than in that of SS. IF staining clarified that CCL18 was specifically highly expressed in LSG of IgG4-RD, compared with those of SS and HC. Macrophages, DCs, B cells, and plasmacytes expressed CCL18 in LSG of IgG4-RD.<br><Conclusion> These results clearly showed that the gene expression pattern in LSG of IgG4-RD is different from that of SS. CCL18 and LTF were identified as disease-related molecules of IgG4-RD.</p>

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