2013 Fiscal Year Annual Research Report
PEG-IFNα/RBV療法のC型肝炎治療効果を予測する新規バイオマーカーの確立
Project/Area Number |
23590553
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Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
黒川 真奈絵 聖マリアンナ医科大学, 医学部, 准教授 (90301598)
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Co-Investigator(Kenkyū-buntansha) |
奥瀬 千晃 聖マリアンナ医科大学, 医学部, 准教授 (00318940)
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Keywords | C型肝炎 / INFα/RBV療法 / 治療効果予測 / バイオマーカー / ペプチドミクス |
Research Abstract |
最終年度は、ペグインターフェロンアルファ/リバビリン(PEG-IFNα/RBV)療法を施行した難治性C型慢性肝炎(iCH-C)患者で、ウイルス学的著効(SVR)または無効(NVR)示した45例のIL-28B rs8099917の遺伝子型を判定した。rs8099917のメジャーホモをSVR予測とし、我々の107個の血清ペプチドイオン強度とヘモグロビン、BMI、年齢を組合せた107P/Hb/BMI/Ageモデル、補体C3fの断片C3f des-arginine(C3f-dR)のイオン強度と血小板数を組合せたC3f-dR/PLTモデルとで、SVR予測能を比較した。IL-28B rs8099917は感度83%、特異度90%、107P/Hb/BMI/Ageモデルは感度77%、特異度90%、C3f-dR/PLTモデルは感度63%、特異度100%と、両モデルともIL-28B rs8099917に比較し感度は低下したが、特異度は同等かそれ以上を示した。3つの方法を組合せると感度100%、特異度90%という非常に高い予測能を示し、我々のモデルがIL-28B遺伝子型で予測出来ない症例を予測することが示された。 同定した5個のC3f由来ペプチドのイオン強度と、PEG-IFNα/RBV療法の効果予測因子である性、年齢、ALT値、血小板数、C型肝炎ウイルス量との相関を107人のiCH-C患者で、肝生検結果との相関を77人の同患者で、IL-28B rs8099917との相関を51人の同患者で検討した。その結果、IL-28B rs8099917とC3f由来15アミノ酸ペプチドのみが相関を示した(p<0.05)。5個のペプチド全てにおいて、イオン強度の高い例はrs8099917のメジャーホモであった。IL-28Bの産生亢進が補体系を活性化し、ウイルス中和能を亢進させる可能性が示された。 以上、血清ペプチド、特にC3f-dRはPEG-IFNα/RBV療法におけるSVRの有用な予測因子であり、補体系がC型肝炎ウイルスの除去に働く可能性が示された。
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Author(s)
Ishizu A, Tomaru U, Murai T, Yamamoto T, Atsumi T, Yoshiki T, Yumura W, Yamagata K, Yamada H, Kumagai S, Kurokawa MS, Suka M, Makino H, Ozaki S.
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PLOS ONE
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Pages: e63182
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[Journal Article] Comparative proteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with polyangiitis.2013
Author(s)
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Noguchi M, Sato T, Nagai K, Utagawa I, Suzuki I, Arito M, Iizuka N, Suematsu N, Okamoto K, Kato T, Yamaguchi N, Kurokawa MS.
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International Journal of Geriatric Psychiatry
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Modern Rheumatology
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[Journal Article] Proteomic analysis of whole glomeruli in patients with IgA nephropathy using micro-sieving.2013
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Kojima S, Koitabashi K, Iizuka N, Okamoto K, Arito M, Sato T, Kurokawa MS, Suematsu N, Shibagaki Y, Yasuda T, Kimura K, Kato T.
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Journal Title
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[Journal Article] Case of Nonalcoholic Steatohepatitis Occurring in Combination with Sleep Apnea Syndrome, Who Showed Improvement of Liver Function by Continuous Positive Airway Pressure.2013
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Shigefuku R, Takahashi H, Ikeda H, Matsunaga K, Koike J, Maeyama S, Matsumoto N, Okuse C, Itoh F, Suzuki M.
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Journal Title
Journal of Clinical Case Reports
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[Journal Article] Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial.2013
Author(s)
Sakaida I, Kawazoe S, Kajimura K, Saito T, Okuse C, Takaguchi K, Okada M, Okita K.
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Journal Title
Hepatology Research
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[Journal Article] High levels of hepatitis B virus after the onset of disease lead to chronic infection in patients with acute hepatitis B.2013
Author(s)
Yotsuyanagi H, Ito K, Yamada N, Takahashi H, Okuse C, Yasuda K, Su¬zuki M, Moriya K, Mizokami M, Miyakawa Y, Koike K.
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Journal Title
Clinical Infectious Diseases
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[Journal Article] Case of Acute Hepatitis B of Genotype H Resulting in Persistent Infection.2013
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Yamada N, Shigefuku R, Sugiyama R, Kobayashi M, Ikeda H, Takahashi H, Okuse C, Suzuki M, Itoh F, Yotsuyanagi H, Yasuda K, Moriya K, Koike K, Wakita T, Kato T.
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Journal Title
World Journal of Gastroenterology
Volume: in press
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[Presentation] Amino acid polymorphisms of Sregion of hepatitis B virus in acute hepatitis B patients in Japan.2013
Author(s)
Yamada N, Sugiyama R, Wakita T, Kato T, Yasuda K, Yotsuyanagi H, Moriya K, Koike K, Okuse C, Suzuki M, Itoh F.
Organizer
The 64th Annual Meeting of the American Association for the Study of Liver Diseases.
Place of Presentation
Washington,D.C.(USA)
Year and Date
20131101-20131105
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[Presentation] Protein profiles of peripheral blood mononuclear cells as a biomarker for Behcet’s Disease.2013
Author(s)
Kurokawa MS, Yoshioka T, Sato T, Nagai K, Iiduka N, Arito M, Takakuwa Y, Nakano H, Ooka S, Suematsu N, Okamoto K, Nakamura H, Suzuki N, Ozaki S, Kato T.
Organizer
American College of Rheumatology. Annual meeting 13
Place of Presentation
San Diego(USA)
Year and Date
20131026-20131030
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[Presentation] Serum peptides, represented by complement 3f des-arginine, are useful for prediction of the response to pegylated interferon-α plus ribavirin in patients with chronic hepatitis C.2013
Author(s)
Noguchi Y, Kurokawa MS, Okuse C, Matsumoto N, Nagai K, Sato T, Arito M, Suematsu N, Okamoto K, Suzuki M, Itoh F, Kato T.
Organizer
HUPO2013
Place of Presentation
Pacifico Yokohama(Kanagawa)
Year and Date
20130914-20130918
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[Presentation] Comparative croteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with polyangiitis.2013
Author(s)
Uchida T, Nagai K, Sato T, IizukaN, Arito M, Takakuwa Y, Nakano H, Ooka S, Kurokawa MS, Suematsu N, Okamoto K, Ozaki S, Kato T.
Organizer
HUPO2013
Place of Presentation
Pacifico Yokohama(Kanagawa)
Year and Date
20130914-20130918
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[Presentation] Protein profiles of peripheral blood mononuclear cells as a biomarker for Behcet’s Disease.2013
Author(s)
Yoshioka T, Kurokawa MS, Sato T, Nagai K, Iizuka N, Arito M, Takakuwa Y, Nakano H, Ooka H, Suematsu N, Okamoto K, Nakamura H, Suzuki N, Ozaki S, Kato T.
Organizer
HUPO2013
Place of Presentation
Pacifico Yokohama(Kanagawa)
Year and Date
20130914-20130918
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[Presentation] Comprehensive analysis of aberrantly glycosylated proteins in rheumatoid arthritis.2013
Author(s)
Sato T, Arito M, Kurokawa MS, Takakuwa Y, Ooka S, Nagai K, Nakamura H, Iizuka N, Suematsu N, Okamoto K, Kato T.
Organizer
HUPO2013
Place of Presentation
Pacifico Yokohama(Kanagawa)
Year and Date
20130914-20130918
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[Presentation] Serum peptide profiles as a candidate biomarker for dementia with lewy bodies.2013
Author(s)
Suzuki I, Kurokawa MS, Noguchi M, Sato T, Utagwa I, Arito M, Iizuka N, Omoteyama K, Suematsu N, Okamoto K, Yamaguchi N, Kato T.
Organizer
HUPO2013
Place of Presentation
Pacifico Yokohama(Kanagawa)
Year and Date
20130914-20130918
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[Presentation] Proteomic analysis of whole glomeruli in patients with IgA nephropathy using micro-sieving.2013
Author(s)
Kojima S, Koitabashi K, Nobuko Iizuka N, Okamoto K, Arito M, Sato T, Kurokawa MS, Suematsu N, Yasuda T, Kimura K, Kato T.
Organizer
HUPO2013
Place of Presentation
Pacifico Yokohama(Kanagawa)
Year and Date
20130914-20130918
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