Identification of novel autoantibodies against cerebral cell surface membrane proteins as biological markers of multiple sclerosis

• Project/Area Number: 20590992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Gifu University
• Principal Investigator: KIMURA Akio Gifu University, 医学部附属病院, 助教 (00362161)
• Co-Investigator(Kenkyū-buntansha): INUZUKA Takashi 岐阜大学, 医学系研究科, 教授 (50184734) ; HOZUMI Isao 岐阜大学, 医学系研究科, 准教授 (20242430) ; TANAKA Yuji 岐阜大学, 医学系研究科, 助教 (70377654)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 脳・神経 / 免疫学 / autoantibody / Heat shock protein 70 / multiple sclerosis (MS) / proteome / Phoshoglyceate mutase 1(PGAMI) / Stress-70 protein(mtHSP70) / 多発性硬化症 / 視神経脊髄炎 / 自己抗体 / Phosphoglycerate mutase 1 / stress 70 protein / 通常型多発性硬化症 / 75 kDa glucose-regulated protein

Research Abstract

We identified the autoantibody against Phosphoglycerate mutase 1 (PGAM 1) and mitochondrial heat shock protein 70 (mtHSP70) in serum from multiple sclerosis (MS) patients by immunoproteomic approach. We tested more samples by one-dimensional immunoblotting of human recombinant PGAM1 and mtHSP70. The prevalence of the anti-PGAM 1 antibody is significantly higher in serum from MS patients (81%) than in serum from other neurological diseases (ONDs) and healthy controls (HCs) (24～32%) (p<0.05). The prevalence of the anti-mtHSP70 antibody is also significantly higher in serum from MS patients (68%) than in serum from ONDs and HCs (20～30%) (p<0.05). We studied the clinical features and magnetic resonance imaging findings of MS patients with these antibodies. As a result, there were no significant differences between these antibodies-positive and -negative MS patients. Additionally, in our comprehensive analysis of the prevalence of both the anti-PGAM1 antibody and the anti-mtHSP70 antibody, the positivity rates of both these antibodies were significantly higher in serum from MS patients (57%) than in serum from patients with ONDs and HCs (0～16%) (p<0.05) ; moreover, the specificity of this combination assay was higher than that of the assay of only one antibody (57% sensitivity ; 93% specificity). Results of our study suggest that the combination of both these antibodies is useful for a more specific diagnosis of MS.

Research Products

• [Journal Article] Antibodies in Patients With Neuropsychiatric Systemic Lupus Erythematosus. (2010)
  • Author(s): Kimura A, Kanoh Y, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
  • Journal Title: Neurology 74 Pages: 1372-1379
  • Peer Reviewed
• [Journal Article] High prevalence of autoantibodies against phosphoglycerate mutase 1 in patients with autoimmune central nervous system diseases. (2010)
  • Author(s): Kimura A, Sakurai T, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M, Inuzuka T
  • Journal Title: J Neuroimmunol. 219 Pages: 105-108
  • Peer Reviewed
• [Journal Article] Motor-dominant chronic inflammatory demyelinating polyneuropathy. (2010)
  • Author(s): Kimura A, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Yoshino H, Yuasa T, Inuzuka T
  • Journal Title: J Neurol. 257 Pages: 621-629
  • Peer Reviewed
• [Journal Article] Antibodies to the GABAB receptor in limbic encephalitis with seizures : case series and characterization of the antigen. (2010)
  • Author(s): Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, Friedman D, Skeen MB, Grisold W, Kimura A, Ohta K, Iizuka T, Guzman M, Graus F, Moss SJ, Balice-Gordon R, Dalmau J
  • Journal Title: Lancet Neurol. 9 Pages: 67-76
  • Peer Reviewed
• [Journal Article] Serial monitoring of basal metabolic rate for therapeutic evaluation in an Issacs' syndrome patient with chronic fluctuating symptoms. (2010)
  • Author(s): Hayashi Y, Kimura A, Watanabe M, Yamada M, Sakurai T, Tanaka Y, Hozumi I, Inuzuka T
  • Journal Title: Internal medicine. 49 Pages: 475-477
  • Peer Reviewed
• [Journal Article] Antibodies in patients with neuropsychiatric systemic lupus erythematosus. (2010)
  • Author(s): Kimura A, Kanoh Y, Saukurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T.
  • Journal Title: Neurology Volume: 74 Pages: 1372-1379
  • Peer Reviewed
• [Journal Article] Motor-dominant chronic inflammatory demyel Mating polyneuropathy. (2010)
  • Author(s): Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Yoshino H, Yuasa T, Inuzuka T.
  • Journal Title: J Neurology Volume: 257 Pages: 621-629
  • Peer Reviewed
• [Journal Article] High prevalence of autoantibodies against phosphoglycerate mutase 1 in patients with autoimmune central nervous system diseases. (2010)
  • Author(s): Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M, Inuzuka T.
  • Journal Title: J Neuroimmunology Volume: 219 Pages: 105-108
  • Peer Reviewed
• [Journal Article] Serial monitoring of basal metabolic rate for therapeutic evaluation in an Issacs' syndrome patient with chronic fluctuating symptoms. (2010)
  • Author(s): Hayashi Y, Kimura A, Watanabe M, Yamada M, Sakurai T, Tanaka Y, Hozumi I, Inuzuka T.
  • Journal Title: Internal medicine Volume: 49 Pages: 475-477
  • Peer Reviewed
• [Journal Article] Markedly ring-enhanced optic nerves due to metastasis of signet-ring cell gastric carcinoma. Internal medicine. (2010)
  • Author(s): Hayashi Y, Sakurai T, Tanaka Y, Yamada M, Koumura A, Kimura A, Hozumi I, Inuzuka T
  • Journal Title: Internal medicine Volume: 49 Pages: 517-517
  • Peer Reviewed
• [Journal Article] Antibodies to the GABAB receptor in limbic encephalitis with seizures : case series and characterization of the antigen. (2010)
  • Author(s): Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, Friedman D, Skeen MB, Grisold W, Kimura A, Ohta K, lizuka T, Guzman M, Graus F, Moss SJ, Balice-Gordon R, Dalmau J.
  • Journal Title: Lancet Neurology Volume: 9 Pages: 67-76
  • Peer Reviewed
• [Journal Article] High levels of copper, zinc, iron and magnesium, but not calcium, in the cerebra spinal fluid of patients with Fahr's disease. (2010)
  • Author(s): Hozumi I, Koumura A, Kimura A, Hasegawa T, Honda A, Hayashi Y, Hashimoto K, Yamada M, Sakurai T, Tanaka Y, Satoh M, Inuzuka T
  • Journal Title: Case Report of Neurology Volume: 2 Pages: 46-51
  • Peer Reviewed
• [Journal Article] 膠原病に伴う神経・筋障害-診断と治療の進歩膠原病における新たな抗神経抗体の検索 (2010)
  • Author(s): 木村暁夫, 犬塚貴
  • Journal Title: 日本内科学会雑誌 Volume: 99 Pages: 115-120
• [Journal Article] 特発性中脳水道狭窄症による閉塞性水頭症に対するV-Pシャント術の1年後から急速に進行するparkinsonismを呈した1例 (2010)
  • Author(s): 櫻井岳郎, 木村暁夫, 山田恵, 林祐一F 田中優司, 保住功, 犬塚貴
  • Journal Title: BRAIN and NERVE Volume: 62 Pages: 527-531
  • Peer Reviewed
• [Journal Article] High prevalence of autoantibodies against phosphoglycerate mutase l in patients with autoimmune central nervous system diseases (2010)
  • Author(s): Kimura A, Sakurai T, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M, Inuzuka T
  • Journal Title: Journal of Neuroimmunology 219 Pages: 105-108
  • Peer Reviewed
• [Journal Article] Antibodies in patients with neuropsychiatric systemic lupus erythematosus (2010)
  • Author(s): Kimura A, Kanoh Y, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
  • Journal Title: Neurology 74 Pages: 1372-1379
  • Peer Reviewed
• [Journal Article] Motor-dominant chronic inflammatory demyelinating polyneuropathy. (2010)
  • Author(s): Kimura A, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Yoshino H, Yuasa T, Inuzuka T
  • Journal Title: Journal of Neurology 257 Pages: 621-629
  • Peer Reviewed
• [Journal Article] Serial monitoring of basal metabolic rate for therapeutic evaluation in an Issacs' syndrome patient with chronic fluctuating symptoms (2010)
  • Author(s): Hayashi Y, Kimura A, Watanabe N, Yamada M, Sakurai T, Tanaka Y, Hozumi I, Inuzuka T
  • Journal Title: Internal medicine 49 Pages: 475-477
  • Peer Reviewed
• [Journal Article] Markedly ring-enhanced optic nerves due to metastasis of signet-ring cell gastric carcinoma (2010)
  • Author(s): Hayashi Y, Sakurai T, Tanaka Y, Yamada M, Koumura A, Kimura A, Hozumi I, Inuzuka T
  • Journal Title: Internal medicine 49 Pages: 517-517
  • NAID: 130000251711
  • Peer Reviewed
• [Journal Article] 胃腸炎後に発症した抗GQ1b抗体陽性の小脳失調症を伴わない急性-側性外転神経麻痺の1例 (2009)
  • Author(s): 櫻井岳郎, 田中優司, 木村暁夫, 保住功, 犬塚貴
  • Journal Title: 神経内科 71 Pages: 514-516
  • Peer Reviewed
• [Journal Article] 胃腸炎後に発症した抗GO1b抗体陽性の小脳失調を伴わない急性一側性外神経麻痺の1例 (2009)
  • Author(s): 櫻井岳郎, 田中優司, 木村暁夫, 保住功, 犬塚貴
  • Journal Title: 神経内科 71 Pages: 514-516
  • Peer Reviewed
• [Journal Article] Creutafddt-Jakob病と類似の臨床経過を示したBasedow病と伴った橋本脳症の1例 (2008)
  • Author(s): 櫻井岳郎, 田中優司, 香村彰宏, 林祐一, 木村暁夫, 保住功, 米田誠, 犬塚貴
  • Journal Title: BRAIN and NERVE 60 Pages: 559-565
  • Peer Reviewed
• [Journal Article] Progressive multifocal leukoencephalopathy and CD4+ T-lymphocytopenia in a patient with Sjogren syndrome. (2008)
  • Author(s): Hayashi Y, Kimura A, Kato S, Koumura A, Sakurai T, Tanaka Y, Hozumi I, Sunden Y, Orba Y, Sawa H, Takahashi H, Inuzuka T
  • Journal Title: J Neural Sci. 268 Pages: 195-198
  • Peer Reviewed
• [Journal Article] Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI. (2008)
  • Author(s): Kimura A, Sakurai T, Tanaka Y, Hozumi I, Takahashi K, Takemura M, Saito K, Seishima M, Inuzuka T
  • Journal Title: Lupus. 17 Pages: 16-20
  • Peer Reviewed
• [Journal Article] Longitudinal analysis of cytokines and chemokines in the cerebrospinal fluid of a patient with neuro-Sweet disease presenting with recurrent encephalomeningitis. (2008)
  • Author(s): Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Nakajima H, Ichiyama T, Inuzuka T
  • Journal Title: Internal Medicine. 47 Pages: 135-141
  • NAID: 130000079753
  • Peer Reviewed
• [Journal Article] Selective cauda equine hypertrophy with idiopathic inflammation. (2008)
  • Author(s): Hayashi Y, Sakurai T, Kimura A, Ikeda T, Matsuyama Z, Suzuki Y, Tanaka Y, Hozumi I, Hosoe H, Takahashi H, Inuzuka T
  • Journal Title: Muscle Nerve. 38 Pages: 1065-1069
  • Peer Reviewed
• [Journal Article] Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on biain MRI. (2008)
  • Author(s): Kimura A, Sakurai T, Tanaka Y, Hozumi I, Takahashi K, Takemura M, Saito K, Seishima M, Inuzuka T.
  • Journal Title: Lupus 17 Pages: 16-20
  • Peer Reviewed
• [Journal Article] Longitudinal analysis of cytokines and chemokines in the cereb rospinal fluid of a patient with neuro-Sweet disease presenting with recurrent encephalomeningitis. (2008)
  • Author(s): Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Nakajima H, lchiyama T, Inuzuka T
  • Journal Title: Internal Medicine 47 Pages: 135-141
  • NAID: 130000079753
  • Peer Reviewed
• [Journal Article] Creutafeldt-Jakob病と禎似の臨床経過を示したBasedow病と伴った橋本脳症の1例 (2008)
  • Author(s): 櫻井岳郎, 田中優司, 香村彰宏, 林祐一, 木村暁夫, 保住功, 米田誠, 犬塚貴
  • Journal Title: BRAIN and NERVE 60 Pages: 559-565
  • Peer Reviewed
• [Journal Article] Identification of antibodies as biological markers in serum from multiple sclerosis patients by immunoproteomic approach.
  • Author(s): Sakurai T, Kimura A, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Inuzuka T
  • Journal Title: J Neuroimmunol. In press.
  • Peer Reviewed
• [Journal Article] Elevated anti-heat shock protein 60 antibody titer is related to white matter hyperintensities.
  • Author(s): Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
  • Journal Title: J Stroke Cerebrovasc Dis. In press.
  • Peer Reviewed
• [Journal Article] Elevated anti-heat shock protein 60 antibody titer is related to white matter hype rintensities.
  • Author(s): Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
  • Journal Title: Journal of stroke cerebrovascular disease Volume: (In press)
  • Peer Reviewed
• [Journal Article] Identification of antibodies as biological markers in serum from multiple sclerosis patients by immunoproteomic approach.
  • Author(s): Sakurai T, Kimura A, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Inuzuka T
  • Journal Title: J Neuroimmunology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Patterns of levels of biological metals in CSF differ among neurodegenerative diseases.
  • Author(s): Hozumi I, Hasegawa T, Honda A, Ozawa K, Hayashi Y, Hashimoto K, Yamada M, Koumura A, Sakurai T, Kimura A, Tanaka Y, Satoh M, Inuzuka T
  • Journal Title: J Neurological Sciences Volume: (In press)
  • Peer Reviewed
• [Presentation] Anti-Endothelial Cell Antibodies in the Elderly with Extended White Matter Hyperintensity. (2011)
  • Author(s): 木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 田中優司, 保住功, 犬塚貴
  • Organizer: American Academy of Neurology 63^<st> Annual Meeting
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2011-04-13
• [Presentation] Stress 70 protein抗体の特異陛に関する検討 (2010)
  • Author(s): 櫻井岳郎、木村暁夫、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第51回日木神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] Motor-dominant CIDP患者の臨床的検討 (2010)
  • Author(s): 木村暁夫、櫻井岳郎、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-21
• [Presentation] プロテオミクス解析を用いた通常型多発性硬化症における疾患特異的抗神経抗体の検索 (2009)
  • Author(s): 櫻井岳郎、木村暁夫、山田恵、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-22
• [Presentation] 抗Hsp60抗体と大脳白質病変に関する研究 (2009)
  • Author(s): 木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20
• [Presentation] Identification of Antibodies Against Brain Antigen in Sera of Patients with Neuropsychiatric Systemic lupus erythematosus. (2009)
  • Author(s): 木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 田中優司, 保住功, 犬塚貴
  • Organizer: American Academy of Neurology 61^<st> Annual Meeting
  • Place of Presentation: Seattle, USA
  • Year and Date: 2009-04-29
• [Presentation] 多発性硬化症患者における抗Phosphoglycerate mutase 1抗体の特異性に関する検討 (2009)
  • Author(s): 木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-13
• [Presentation] プロテオミクス解析を用いた通常型多発性硬化症における疾患特異的抗神経抗体の検索 (2009)
  • Author(s): 櫻井岳郎、木村暁夫、山田恵、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-13
• [Presentation] 多発性硬化症患者こおける抗Phosphoglycerate mutase 1抗体の特異性に関する検討 (2009)
  • Author(s): 木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 木村暁夫, 保住功, 米田誠, 犬塚貴
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-13
• [Presentation] 通常型多発性硬化症における抗 (2008)
  • Author(s): 櫻井岳郎、木村暁夫、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] CNSループス患者におけるプロテオミクス解析を用いた自己抗体認識抗原の同定 (2008)
  • Author(s): 木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] CNSルーフス患者におけるフロテオミクス解析を川いた自己抗体認識抗原の同定 (2008)
  • Author(s): 木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 木村暁夫, 保住功, 米田誠, 犬塚貴
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] プロテオミクス解析を用いた中枢神経ループス特異的抗神経抗体の検索 (2008)
  • Author(s): 木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
  • Organizer: 第20回日本神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-18
• [Presentation] フロテオミクス解析を用いた中枢神経ループス特異的抗神経抗体の検索 (2008)
  • Author(s): 木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 木村暁夫, 保住功, 米田誠, 犬塚貴
  • Organizer: 第20回日本陣経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-18
• [Remarks] ホームページ等