Genetic Association Study on HLA with Interstitial Lung Diseases in Rheumatoid Arthritis Patients.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791018
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: HASHIMOTO Atsushi 独立行政法人国立病院機構(相模原病院臨床研究センター), その他部局等, その他 (50327376)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 関節リウマチ / 間質性肺病変 / HLA

Research Abstract

Interstitial lung disease is a critical complication associated with rheumatoid arthritis (RA). Methotrexate-induced interstitial lung disease (MI-ILD) can occur in RA patients and represents a potentially life-threatening drug hypersensitivity reaction. It is believed that Japanese RA patients are more susceptible to MI-ILD than other ethnic groups. Striking association of human leukocyte antigen (HLA) class I alleles with severe cutaneous adverse reactions has recently been reported for many drugs. Here, we investigated the association of HLA with ILD in RA. HLA-DRB1*04, shared epitope (SE) and DQB1*04 were associated with significantly decreased risk of ILD. In contrast, DRB1*16, DR2 serological group and DQB1*06 were significantly associated with risk of ILD. We found a highly significant association of the A*31:01 allele with MI-ILD.

Research Products

• [Journal Article] 関節リウマチにおけるリポキシゲナーゼの役割 (2014)
  • Author(s): 遠藤平仁, 橋本篤
  • Journal Title: 臨床リウマチ Volume: 26(1) Pages: 9-16
• [Journal Article] HLA-DRB1*08 : 02 is associated with bucillamine-induced proteinuria in Japanese rheumatoid arthritis patients (2014)
  • Author(s): Furukawa H, Oka S, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Miyashita T, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S
  • Journal Title: Biomark Insights Volume: (in press)
• [Journal Article] Human Leukocyte Antigens and Systemic Lupus Erythematosus : A Protective Role for the HLA-DR6 alleles DRB1*13:02 and *14:03 (2014)
  • Author(s): Furukawa H, Kawasaki A, Oka S, Ito I, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Kondo Y, Ito S, Hayashi T, Matsumoto I, Kusaoi M, Amano H, Nagai T, Hirohata S, Setoguchi K, Kono H, Okamoto A, Chiba N, Suematsu E, Katayama M, Migita K, Suda A, Ohno S, Hashimoto H, Takasaki Y, Sumida T, Nagaoka S, Tsuchiya N, Tohma S
  • Journal Title: PLoS One Volume: 9(2) Pages: e87792
• [Journal Article] Neutrophil CD64 for monitoring the activity of nontuberculous mycobacteria infection in patients with rheumatoid arthritis (2014)
  • Author(s): Komiya A, Matsui T, Horie K, Fukuda H, Nogi S, Iwata K, Tsuno H, Ogihara H, Futami H, Ikenaka T, Kawakami M, Furukawa H, Hashimoto A, Tohma S
  • Journal Title: Mod Rheumatol Volume: (in press)
• [Journal Article] A case of granulomatosis with polyangiitis (Wegener's granulomatosis) manifested with asymptomatic intracerebral hemorrhage (2013)
  • Author(s): Takaoka H, Hashimoto A, Nogi S, Iwata K, Futami H, Arinuma Y, Shimada K, Nakayama H, Komiya A, Furukawa H, Matsui T, Tohma S
  • Journal Title: Nihon Rinsho Meneki Gakkai Kaishi Volume: 36(1) Pages: 58-61
• [Journal Article] Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus (2013)
  • Author(s): Furukawa H, Kawasaki A, Oka S, Shimada K, Matsui T, Ikenaka T, Hashimoto A, Okazaki Y, Takaoka H, Futami H, Komiya A, Kondo Y, Ito S, Hayashi T, Matsumoto I, Kusaoi M, Takasaki Y, Nagai T, Hirohata S, Setoguchi K, Suda A, Nagaoka S, Kono H, Okamoto A, Chiba N, Suematsu E, Fukui N, Hashimoto H, Sumida T, Ono M, Tsuchiya N, Tohma S
  • Journal Title: Lupus Volume: 22(5) Pages: 497-503
• [Journal Article] Association of increased frequencies of HLA-DPB1*05 : 01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients (2013)
  • Author(s): Furukawa H, Oka S, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Nagai T, Hirohata S, Setoguchi K, Okamoto A, Chiba N, Suematsu E, Miyashita T, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S
  • Journal Title: PLoS One Volume: 8(1) Pages: e53910
• [Journal Article] Genome, epigenome and transcriptome analyses of a pair of monozygotic twins discordant for systemic lupus erythematosus (2013)
  • Author(s): Furukawa H, Oka S, Matsui T, Hashimoto A, Arinuma Y, Komiya A, Fukui N, Tsuchiya N, Tohma S
  • Journal Title: Hum Immunol Volume: 74(2) Pages: 170-5
• [Journal Article] HLA-A*31:01 and methotrexate-induced interstitial lung disease in Japanese rheumatoid arthritis patients : A multi-drug hypersensitivity marker? (2013)
  • Author(s): Furukawa H, Oka S, Shimada K, Rheumatoid Arthritis associated Interstitial Lung Disease (RA-ILD) Study Consortium, Tsuchiya N, Tohma S
  • Journal Title: Ann Rheum Dis Volume: 72(1) Pages: 153-5
• [Journal Article] Role of FK506 binding protein 5 (FKBP5) in osteoclast differentiation (2013)
  • Author(s): Kimura M, Nagai T, Matsushita R, Hashimoto A, Miyashita T, Hirohata S
  • Journal Title: Mod Rheumatol Volume: 23(6) Pages: 1133-9
• [Journal Article] Clinical features of 405 Japanese patients with systemic sclerosis (2012)
  • Author(s): Hashimoto A, Endo H, Kondo H, Hirohata S
  • Journal Title: Mod Rheumatol Volume: 22(2) Pages: 272-9
• [Journal Article] Incidence and the risk factor of malignancy in Japanese patients with systemic sclerosis (2012)
  • Author(s): Hashimoto A, Arinuma Y, Nagai T, Tanaka S, Matsui T, Tohma S, Endo H, Hirohata S
  • Journal Title: Intern Med Volume: 51(13) Pages: 1683-8
• [Journal Article] Case of immunosuppressant-resistant amyopathic dermatomyositis with rapidly progressive interstitial pneumonia ameliorated after resection of gastric cancer (2012)
  • Author(s): Nogi S, Hashimoto A, Iwata K, Futami H, Takaoka H, Arinuma Y, Shimada K, Nakayama H, Matsui T, Komiya A, Furukawa H, Tamama S, Kinoshita S, Moriya H, Tohma S
  • Journal Title: Nihon Rinsho Meneki Gakkai Kaishi Volume: 35(3) Pages: 188-93
• [Journal Article] Neutrophil CD64 is upregulated in patients with active adult-onset Still's disease (2012)
  • Author(s): Komiya A, Matsui T, Nogi S, Iwata K, Futami H, Takaoka H, Arinuma Y, Hashimoto A, Shimada K, Ikenaka T, Nakayama H, Furukawa H, Tohma S
  • Journal Title: Scand J Rheumatol Volume: 41(2) Pages: 156-8
• [Journal Article] Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis : A protective role for shared epitope (2012)
  • Author(s): Furukawa H, Oka S, Shimada K, Sugii S, Ohashi J, Matsui T, Ikenaka T, Nakayama H, Hashimoto A, Takaoka H, Arinuma Y, Okazaki Y, Futami H, Komiya A, Fukui N, Nakamura T, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S
  • Journal Title: PLoS One Volume: 7(5) Pages: e33133
• [Journal Article] 強皮症と悪性腫瘍 (2012)
  • Author(s): 橋本篤, 遠藤平仁
  • Journal Title: リウマチ科 Volume: 48(4) Pages: 379-384
• [Presentation] Analysis of the Factors That Contribute to the Differences Between DAS28-ESR and DAS28-CRP (2013)
  • Author(s): Matsui T, Tsuno H, Nishino J, Kuga Y, Hashimoto A, Tohma S
  • Organizer: ACR/ARHP Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20131026-30
• [Presentation] Incidence Of Malignancy In Patients With Rheumatoid Arthritis From a Japanese Large Observational Cohort (NinJa) (2013)
  • Author(s): Hashimoto A, Chiba N, Nishino J, Matsui T, Tohma S
  • Organizer: ACR/ARHP Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20131026-30
• [Presentation] 2003-2011年度のNinJa コホートを用いた関節リウマチ患者における悪性疾患の検討 (2013)
  • Author(s): 橋本篤, 千葉実行, 角田慎一郎, 松井利浩, 西野仁樹, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] 当院関節リウマチ患者における顎骨壊死およびビスホスホネート関連顎骨壊死の疫学的検討 (2013)
  • Author(s): 川上美里, 二見秀一, 堀江孝一郎, 福田英史, 野木真一, 津野宏隆, 岩田香奈子, 池中達央, 橋本篤, 小宮明子, 古川宏, 中山久徳, 松井利浩, 西野仁樹, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] 関節リウマチ患者におけるTocilizumab 投与間隔延長の検討 (2013)
  • Author(s): 福田英史, 橋本篤, 堀江孝一郎, 野木真一, 岩田香奈子, 二見秀一, 川上美里, 津野宏隆, 小宮明子, 古川宏, 松井利浩, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] チロシンキナーゼ阻害剤イマチニブが有効であった関節リウマチの1例 (2013)
  • Author(s): 二見秀一, 橋本篤, 堀江孝一郎, 福田英史, 野木真一, 津野宏隆, 岩田香奈子, 川上美里, 松井利浩, 池中達央, 早川洋美, 小宮明子, 古川宏, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] 成人関節リウマチ患者における体重当たりのMTX量に関する検討 (2013)
  • Author(s): 松井利浩, 津野宏隆, 橋本篤, 末永康夫, 岸本暢将, 西野仁樹, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] NinJa2011 を利用したDAS28-ESR とDAS28-CRP の差に影響を及ぼす因子の検討 (2013)
  • Author(s): 松井利浩, 西野仁樹, 久我芳昭, 津野宏隆, 橋本篤, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] アダリムマブ開始時のメトトレキサート併用用量が治療効果に及ぼす影響 (2013)
  • Author(s): 岩田香奈子, 松井利浩, 堀江孝一郎, 福田英史, 野木真一, 津野宏隆, 二見秀一, 川上美里, 池中達央, 橋本篤, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] PET, ガリウムシンチグラフィー, 造影CT 検査でも検出不能であった進行卵巣癌による傍腫瘍症候群の一例 (2013)
  • Author(s): 野木真一, 堀江孝一郎, 福田英史, 岩田香奈子, 二見秀一, 川上美里, 小宮明子, 橋本篤, 松井利浩, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] 関節リウマチ患者における生体電気インピーダンス法を用いた筋肉量の測定 (2013)
  • Author(s): 野木真一, 堀江孝一郎, 福田英史, 岩田香奈子, 二見秀一, 川上美里, 小宮明子, 橋本篤, 松井利浩, 古川宏, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] 関節リウマチにおけるBMI と疾患活動性の関係 (2013)
  • Author(s): 津野宏隆, 松井利浩, 橋本篤, 西野仁樹, 當間重人
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都
  • Year and Date: 20130418-20
• [Presentation] 当院におけるゴリムマブ投与例の臨床的検討 (2013)
  • Author(s): 橋本篤, 堀江孝一郎, 福田英史, 岩田香奈子, 二見秀一, 荻原秀樹, 川上美里, 松井利浩 and 當間重人
  • Organizer: 第28回日本臨床リウマチ学会
  • Place of Presentation: 千葉
  • Year and Date: 2013-11-30
• [Presentation] 関節リウマチ患者における感染症リスク因子の検討 (2013)
  • Author(s): 橋本篤, 川上美里, 松井利浩, 當間重人
  • Organizer: 第41回日本臨床免疫学会総会
  • Place of Presentation: 下関
  • Year and Date: 2013-11-27
• [Presentation] リウマチ科における血漿中(1→3)- β-D-グルカン測定と陽性例の検討 (2012)
  • Author(s): 橋本篤, 堀江孝一郎, 福田英史, 野木真一, 岩田香奈子, 二見秀一, 川上美里, 津野宏隆, 小宮明子, 古川宏, 松井利浩, 當間重人
  • Organizer: 第66回国立病院総合医学会
  • Place of Presentation: 神戸
  • Year and Date: 20121116-17
• [Presentation] THE CLINICAL UTILITY OF CD64 EXPRESSION ON NEUTROPHIL IN ACUTE-ONSET INTERSTITIAL LUNG DAMAGE COMPLICATED IN PATIENTS WITH RHEUMATOID ARTHRITIS (2012)
  • Author(s): Arinuma Y, Matsui T, Komiya A, Nogi S, Iwata K, Futami H, Takaoka H, Hashimoto A, Nakayama H, Tohma S
  • Organizer: EULAR Congress
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20120606-09
• [Presentation] BEING UNDERWEIGHT IS ASSOCIATED WITH HIGH DISEASE ACTIVITY AND INCREASED RISK FOR HOSPITALIZATION IN PATIENTS WITH RHEUMATOID ARTHRITIS (2012)
  • Author(s): Matsui T, Nishino J, Kuga Y, Tsuno H, Hashimoto A, Tohma S
  • Organizer: EULAR Congress
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20120606-09
• [Presentation] 関節リウマチ患者に生じた急性間質性肺障害の臨床的診断と好中球CD64 分子発現数との関係 (2012)
  • Author(s): 有沼良幸, 松井利浩, 小宮明子, 堀江孝一郎, 野木真一, 岩田香奈子, 二見秀一, 高岡宏和, 橋本篤, 中山久徳, 當間重人
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] 難治性下腿蜂窩織炎の加療中に好中球CD64 の著明な上昇より粟粒結核を診断しえた関節リウマチの一例 (2012)
  • Author(s): 野木真一, 有沼良幸, 石川雄一, 松井利浩, 小宮明子, 二見秀一, 高岡宏和, 橋本篤, 中山久徳, 當間重人
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] トシリズマブによる治療中にレジオネラ肺炎を発症した関節リウマチの一例 (2012)
  • Author(s): 石川雄一, 有沼良幸, 野木真一, 中山久徳, 橋本篤, 小宮明子, 松井利浩, 當間重人
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] 生物製剤投与例を含む関節リウマチ患者における肺炎入院例の検討 (2012)
  • Author(s): 橋本篤, 松井利浩
  • Organizer: 第86回日本感染症学会学術講演会
  • Place of Presentation: 長崎
  • Year and Date: 20120426-28
• [Presentation] アダリムマブ導入時メトトレキサートは8mg/w 超での併用がより有用である (2012)
  • Author(s): 岩田香奈子, 松井利浩, 堀江孝一郎, 福田英史, 野木真一, 津野宏隆, 二見秀一, 川上美里, 池中達央, 橋本篤, 當間重人
  • Organizer: 第27回日本臨床リウマチ学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-11-23