Immuno-genetic approaches for investigation of pathogenesis of new disease entity "IgG4-related disease"

• Project/Area Number: 25870087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology; Pathobiological dentistry/Dental radiology
• Research Institution: University of Tsukuba
• Principal Investigator: TSUBOI Hiroto 筑波大学, 医学医療系, 講師 (80580505)
• Co-Investigator(Renkei-kenkyūsha): NAKAI Yuji 弘前大学, 食料科学研究所, 教授 (10321788)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IgG4関連疾患 / シェーグレン症候群 / DNAマイクロアレイ / 口唇唾液腺 / CCL18

Outline of Final Research Achievements

The gene expressions in LSGs were compared between IgG4-RD (N=5), SS (N=5), and HC (N=3) by DNA microarray. Clustering by principal component analysis (PCA), and pairwise comparison between IgG4-RD and SS were performed. We conducted validation by qPCR for identified candidate genes among up-regulated DEGs in IgG4-RD using RNA isolated from LSGs of IgG4-RD (N=9), SS (N=10), and HC (N=4) other than patients examined by DNA microarray. The expression of CCL18 and expressing cells in LSGs were compared between IgG4-RD, SS, and HC by immunofluorescence (IF) staining. Gene expression patterns in IgG4-RD, SS, and HC were quite different in PCA. 1321 up-regulated DEGs and　1320 down-regulated DEGs in IgG4-RD compared with SS were identified in pairwise comparison. We validated significantly higher expression of CCL18 in LSGs of IgG4-RD than in SS and HC (P<0.05) by qPCR. IF staining clarified that many CD68 positive macrophages expressed CCL18 in LSGs of IgG4-RD whereas not in SS and HC.

Research Products

• [Journal Article] Clinical features of patients with IgG4-related disease complicated with perivascular lesions (2015)
  • Author(s): Ebe H, Tsuboi H, Hagiya C, Takahashi H, Yokosawa M, Hagiwara S, Hirota T, Kurashima Y, Takai C, Miki H, Asashima H, Umeda N, Kondo Y, Ogishima H, Suzuki T, Chino Y, Matsumoto I, Sumida T
  • Journal Title: Modern Rheumatology Volume: 25 Pages: 105-109
  • Peer Reviewed
• [Journal Article] DNA microarray analysis of labial salivary glands in IgG4-related disease. Comparison with Sjogren's syndrome (2014)
  • Author(s): Tsuboi H, Nakai Y, Iizuka M, Asashima H, Hagiya C, Tsuzuki S, Hirota T, Miki H, Hagiwara S, Kondo Y, Tanaka A, Moriyama M, Matsumoto I, Nakamura S, Yoshihara T, Abe K, Sumida T
  • Journal Title: Arthritis and Rheumatology Volume: 66 Pages: 2892-2899
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinicopathological features of IgG4-related disease complicated with orbital involvement (2014)
  • Author(s): Hagiya C, Tsuboi H, Yokosawa M, Hagiwara S, Takai C, Hirota T, Asashima H, Miki H, Umeda N, Horikoshi M, Kondo Y, Sugihara M, Ogishima H, Suzuki T, Hiraoka T, Kaji Y, Matsumoto I, Ohshika T, Sumida T
  • Journal Title: Modern Rheumatology Volume: 24 Pages: 471-476
  • Peer Reviewed
• [Journal Article] Clinicopathological features of IgG4-related disease complicated with orbital involvement (2014)
  • Author(s): Hagiya C, Tsuboi H, Yokosawa M, Hagiwara S, Takai C, Hirota T, Asashima H, Miki H, Umeda N, Horikoshi M, Kondo Y, Sugihara M, Ogishima H, Suzuki T, Hiraoka T, Kaji Y, Matsumoto I, Ohshika T, Sumida T
  • Journal Title: Mod Rheumatol Volume: in press
  • Peer Reviewed
• [Journal Article] Clinical features of patients with IgG4-related disease complicated with perivascular lesions (2014)
  • Author(s): Ebe H, Tsuboi H, Hagiya C, Takahashi H, Yokosawa M, Hagiwara S, Hirota T, Kurashima Y, Takai C, Miki H, Asashima H, Umeda N, Kondo Y, Ogishima H, Suzuki T, Chino Y, Matsumoto I, Sumida T
  • Journal Title: Mod Rheumatol Volume: in press
  • Peer Reviewed
• [Presentation] Up-regulation of CCL18-CCR8 signaling in patients with IgG4-related disease (2015)
  • Author(s): Hiroto Tsuboi, Mana Iizuka, Hiromitsu Asashima, Hiroyuki Takahashi, Tomoya Hirota, Yuya Kondo, Isao Matsumoto, Takayuki Sumida
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] DNAマイクロアレイによるIgG4関連疾患の口唇唾液腺における遺伝子発現解析 (2014)
  • Author(s): 坪井洋人、中井雄治、飯塚麻菜、浅島弘充、高橋広行、廣田智哉、近藤裕也、古川祥子、田中昭彦、森山雅文、松本功、吉原俊雄、中村誠司、阿部啓子、住田孝之
  • Organizer: 第23回日本シェーグレン症候群学会
  • Place of Presentation: 長崎
  • Year and Date: 2014-09-12 – 2014-09-13
• [Presentation] IgG4関連疾患とシェーグレン症候群の口唇唾液腺におけるDNAマイクロアレイによる遺伝子発現 (2014)
  • Author(s): 坪井洋人、中井雄治、飯塚麻菜、浅島弘充、萩谷千裕、都築清歌、廣田智哉、近藤裕也、田中昭彦、森山雅文、松本功、中村誠司、吉原俊雄、阿部啓子、住田孝之
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Book] ケモカインとIgG4関連疾患、IgG4研究会モノグラフ (2015)
  • Author(s): 坪井洋人、中井雄治、飯塚麻菜、森山雅文、吉原俊雄、中村誠司、阿部啓子、住田孝之
  • Total Pages: 6
  • Publisher: 前田書店