Analysis of risk factors associated with non-response to infliximab treatment for Behcet's disease

• Project/Area Number: 23659815
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Yokohama City University
• Principal Investigator: MIZUKI Nobuhisa 横浜市立大学, 医学研究科, 教授 (90336579)
• Co-Investigator(Kenkyū-buntansha): MEGURO Akira 横浜市立大学, 医学研究科, 特任講師 (60508802) ; KAWAGOE Tatsukata 横浜市立大学, 医学部, 助教 (20564800)
• Co-Investigator(Renkei-kenkyūsha): SAWASAKI Tatsuya 愛媛大学, 無細胞生命科学工学研究センター, 教授 (50314969)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 眼生化学 / 分子生物学 / ベーチェット病 / インフリキシマブ / 薬剤応答 / 自己抗体

Research Abstract

The aim of this study was to investigate risk factors associated with non-response to infliximab treatment for Behcet’s disease. We found some candidate proteins associated with non-response to infliximab treatment using wheat cell-free protein synthesis technology. In addition, we found some candidate genes for non-response to infliximab treatment by assessing the genotypic data from the genome-wide association study.

Research Products

• [Journal Article] Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease (2013)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: Ann Rheum Dis
  • URL: http://ard.bmj.com/content/early/2013/02/24/annrheumdis-2011-200288.long
  • Peer Reviewed
• [Journal Article] Staining internal limiting membrane with a mixture of BBG and sodium hyaluronate (2013)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: Br J Ophthalmol Volume: 97 Issue: 6 Pages: 690-3
  • DOI: 10.1136/bjophthalmol-2012-302289
  • Peer Reviewed
• [Journal Article] A case of corneal endotheliitis with mumps virus RNA in aqueous humor detected by rt-PCR (2013)
  • Author(s): Mizuki N
  • Journal Title: Ocul Immunol Inflamm. Volume: 21 Issue: 2 Pages: 150-2
  • DOI: 10.3109/09273948.2012.747619
  • Peer Reviewed
• [Journal Article] Acute retinal necrosis: factors associated with anatomic and visual outcomes. (2013)
  • Author(s): Mizuki N
  • Journal Title: Jpn J Ophthalmol Volume: 57 Issue: 1 Pages: 98-103
  • DOI: 10.1007/s10384-012-0211-y
  • NAID: 10031168363
  • Peer Reviewed
• [Journal Article] Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behcet disease. (2013)
  • Author(s): Kirino Y
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Investigation of the Association Between Toll-like Receptor 9 Gene Polymorphisms and Sarcoidosis in Japanese Patients. (2013)
  • Author(s): Yotsumoto S
  • Journal Title: Ocular Immunology and Inflammation Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population. (2013)
  • Author(s): Mikami T
  • Journal Title: Molecular Vision Volume: 19 Pages: 845-851
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease. (2013)
  • Author(s): Lee YJ
  • Journal Title: Annals of the Rheumatic Diseases Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1 (2012)
  • Author(s): Mizuki N, Meguro A
  • Journal Title: Nat Genet Volume: 45 Issue: 2 Pages: 202-7
  • DOI: 10.1038/ng.2520
  • Peer Reviewed
• [Journal Article] Modification of Swan-Jacobs lens for iridocorneal angle surgery (2012)
  • Author(s): Meguro A, Mizuki N(他 2名)
  • Journal Title: Graefes Arch Clin Exp Ophthalmol
  • URL: http://link.springer.com/article/10.1007%2Fs00417-012-2232-0
  • Peer Reviewed
• [Journal Article] Modulation of human visual evoked potentials in 3-dimensional perception after stimuli produced with an integral imaging method (2012)
  • Author(s): Mizuki N
  • Journal Title: Clin EEG Neurosci Volume: 43 Issue: 4 Pages: 303-11
  • DOI: 10.1177/1550059412445608
  • Peer Reviewed
• [Journal Article] Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles (2012)
  • Author(s): Ota M, Meguro A, Kawagoe T, Mizuki N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Issue: 11 Pages: 7109-15
  • DOI: 10.1167/iovs.12-10491
  • Peer Reviewed
• [Journal Article] Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina (2012)
  • Author(s): Meguro A, Ota M, Kawagoe T, Mizuki N
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e39300-e39300
  • DOI: 10.1371/journal.pone.0039300
  • Peer Reviewed
• [Journal Article] Genetic variants on chromosome 1q41 influence ocular axial length and high myopia (2012)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: PLoS Genet Volume: 8 Issue: 6 Pages: e1002753-e1002753
  • DOI: 10.1371/journal.pgen.1002753
  • Peer Reviewed
• [Journal Article] Immediate removal of posteriorly dislocated lens fragments through sclerocorneal incision during cataract surgery (2012)
  • Author(s): Kawagoe T, Mizuki N
  • Journal Title: Br J Ophthalmol Volume: 96 Issue: 8 Pages: 1058-62
  • DOI: 10.1136/bjophthalmol-2011-300864
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients (2012)
  • Author(s): Meguro A, Mizuki N(他 15 名)
  • Journal Title: Mol Vis Volume: 18 Pages: 512-8
  • URL: http://www.molvis.org/molvis/v18/a56/
  • Peer Reviewed
• [Journal Article] Infliximab monotherapy versus infliximab and colchicine combination therapy in patients with Behcet's disease (2012)
  • Author(s): Kawagoe T, Mizuki N
  • Journal Title: Ocul Immunol Inflamm Volume: 20 Issue: 3 Pages: 193-7
  • DOI: 10.3109/09273948.2012.665124
  • Peer Reviewed
• [Journal Article] Confirmation of TBK1 duplication in normal tension glaucoma (2012)
  • Author(s): Kawase K, et al
  • Journal Title: Experimental Eye Research Volume: 96 Issue: 1 Pages: 178-180
  • DOI: 10.1016/j.exer.2011.12.021
  • Peer Reviewed
• [Journal Article] Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population (2012)
  • Author(s): Horie Y, et al
  • Journal Title: Rheumatology Volume: (印刷中) Issue: 6 Pages: 983-6
  • DOI: 10.1093/rheumatology/ker444
  • Peer Reviewed
• [Journal Article] Thermocautery for inferior conjunctivochalasis (2012)
  • Author(s): Mizuki N
  • Journal Title: Cornea Volume: 31 Issue: 5 Pages: 514-9
  • DOI: 10.1097/ico.0b013e3181dc81d2
  • Peer Reviewed
• [Journal Article] Cyclooxygenase inhibitor improved an exudative lesion of choroidal neovascularization in age-related macular degeneration (2012)
  • Author(s): Mizuki N(他 5名)
  • Journal Title: Eur J Ophthalmol Volume: 22(3) Issue: 3 Pages: 495-8
  • DOI: 10.5301/ejo.5000032
  • Peer Reviewed
• [Journal Article] Anatomical and functional changes of retina following subretinal injection of high-speed fluid (2012)
  • Author(s): Uemoto R, et al
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: 250 Issue: 3 Pages: 447-450
  • DOI: 10.1007/s00417-011-1800-z
  • Peer Reviewed
• [Journal Article] Factors associated with enlargement of chorioretinal atrophy after intravitreal bevacizumab for myopic choroidal neovascularization (2012)
  • Author(s): Uemoto R, et al
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: (印刷中) Issue: 7 Pages: 989-97
  • DOI: 10.1007/s00417-011-1921-4
  • Peer Reviewed
• [Journal Article] The carboxyl-terminal region of Crtac1B/LOTUS acts as a functional domain in endogenous antagonism to Nogo receptor-1 (2012)
  • Author(s): Mizuki N
  • Journal Title: Biochem Biophys Res Commun Volume: 418 Issue: 2 Pages: 390-5
  • DOI: 10.1016/j.bbrc.2012.01.033
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients. (2012)
  • Author(s): Sakuyama K
  • Journal Title: Molecular Vision Volume: 18 Pages: 512-518
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients (2012)
  • Author(s): Sakuyama K, Meguro A, Ota M, Ishihara M, Uemoto R, Ito H, Okada E, Namba K, Kitaichi N, Morimoto S, Kaburaki T, Ando Y, Takenaka S, Yuasa T, Ohno S, Inoko H, Mizuki N
  • Journal Title: Molecular Vision Volume: 18 Pages: 512-518
  • Peer Reviewed
• [Journal Article] Sarcoidosis (2011)
  • Author(s): Kawagoe T.Mizuki N
  • Journal Title: Curr Opin Ophthalmol Volume: 22 Issue: 6 Pages: 502-7
  • DOI: 10.1097/icu.0b013e32834bbd7e
  • Peer Reviewed
• [Journal Article] Clinical Course before and after Cataract and Glaucoma Surgery under Systemic Infliximab Therapy in Patients with Behcet's Disease (2011)
  • Author(s): Mizuki N
  • Journal Title: Case Rep Ophthalmol Volume: 2 Issue: 2 Pages: 189-92
  • DOI: 10.1159/000329190
  • Peer Reviewed
• [Journal Article] Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients (2011)
  • Author(s): Ito Ryuta; Ota Masao; Meguro Akira, et al
  • Journal Title: OCULAR IMMUNOLOGY AND INFLAMMATION Volume: 19:3 Issue: 3 Pages: 202-205
  • DOI: 10.3109/09273948.2011.553981
  • Peer Reviewed
• [Journal Article] Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma (2011)
  • Author(s): Meguro A, Mizuki N(他 26 名)
  • Journal Title: Mol Vis Volume: 17 Pages: 792-6
  • URL: http://www.molvis.org/molvis/v17/a89/
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population (2011)
  • Author(s): Kawagoe T, Meguro A, Mizuki N(他 12名)
  • Journal Title: Mol Vis Volume: 17 Pages: 731-6
  • URL: http://www.molvis.org/molvis/v17/a83/
  • Peer Reviewed
• [Journal Article] Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis (2011)
  • Author(s): Mizuki N
  • Journal Title: J Hum Genet Volume: 56 Issue: 3 Pages: 196-9
  • DOI: 10.1038/jhg.2010.159
  • NAID: 10030658234
  • Peer Reviewed
• [Journal Article] Association analysis of Toll-like receptor 7 gene polymorphisms and Behcet's disease in Japanese (2011)
  • Author(s): Sada T, et al
  • Journal Title: Human Immunology Volume: 72 Issue: 3 Pages: 269-272
  • DOI: 10.1016/j.humimm.2010.12.007
  • Peer Reviewed
• [Journal Article] Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma (2011)
  • Author(s): Yasumura R, Meguro A, Ota M, Nomura E, Uemoto R, Kashiwagi K, et al
  • Journal Title: Molecular Vision Volume: 17 Pages: 792-796
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese (2011)
  • Author(s): Sato M, Kawagoe T, Meguro A, Ota M, Katsuyama Y, Ishihara M, Namba K, Kitaichi N, Morimoto S, Kaburaki T, Ando Y, Takenaka S, Ohno S, Inoko H, Mizuki N
  • Journal Title: Molecular Vision Volume: 17 Pages: 731-736
  • Peer Reviewed
• [Journal Article] Treatment of pterygium by ligation and bevacizumab injection (2010)
  • Author(s): Mizuki N
  • Journal Title: Cornea Volume: 31 Issue: 11 Pages: 1339-41
  • DOI: 10.1097/ico.0b013e3182408bc7
  • Peer Reviewed
• [Presentation] Genome-wide association studies on multifactorial ocular diseases (2011)
  • Author(s): Mizuki N Meguro A
  • Organizer: 52nd Annual Meeting of Taiwan Ophthalmological Society(招待講演)
  • Place of Presentation: 台湾・台北市
• [Presentation] Molecular genetics of Behcet's disease (2011)
  • Author(s): Mizuki N, Meguro A, Mochizuki M, Ohno S, Inoko H
  • Organizer: The 11th International Ocular Inflammation Society(招待講演)
  • Place of Presentation: インド・ゴア
• [Presentation] Behcet's disease: Role of regulatory T cells in disease remission (2011)
  • Author(s): Mizuki N, Meguro A, Asukata Y, Masaki Takeuchi, Ohno S, Mochizuki M, Inoko H
  • Organizer: The 11th International Ocular Inflammation Society(招待講演)
  • Place of Presentation: インド・ゴア