Kikuchi, Jun



School of Medicine, Department of Internal Medicine (Rheumatology) (Shinanomachi)




Research Areas 【 Display / hide

  • Life Science / Connective tissue disease and allergy

Research Keywords 【 Display / hide

  • Systemic lupus erythematosus

  • Rheumatoid arthritis


Papers 【 Display / hide

  • Initial predictors of poor survival in myositisassociated interstitial lung disease: A multicentre cohort of 497 patients

    Sato S., Masui K., Nishina N., Kawaguchi Y., Kawakami A., Tamura M., Ikeda K., Nunokawa T., Tanino Y., Asakawa K., Kaneko Y., Gono T., Ukichi T., Kaieda S., Naniwa T., Kuwana M., Okano Y., Yamaguchi Y., Taniguchi Y., Kikuchi J., Kubo M., Watanabe M., Harada T., Kazuyori T., Kameda H., Kaburaki M., Matsuzawa Y., Yoshida S., Yoshioka Y., Hirai T., Wada Y., Ishii K., Fujiwara S., Saraya T., Morimoto K., Hara T., Suzuki H., Shibuya H., Muro Y., Aki R., Shibayama T., Ohshima S., Yasuda Y., Terada M., Kawahara Y.

    Rheumatology (United Kingdom) (Rheumatology (United Kingdom))  57 ( 7 ) 1212 - 1221 2018.07

    ISSN  14620324

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    © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. Objective. To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). Methods. We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositisassociated ILD, JAMI). Inclusion criteria were an onset age ≥16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. Results. JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ≥60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ≥1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). Conclusion. We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality.

  • Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis

    Kikuchi J., Kondo T., Shibata A., Sakai R., Okada Y., Chino K., Okuyama A., Kurasawa T., Takei H., Amano K.

    Modern Rheumatology (Modern Rheumatology)  28 ( 3 ) 444 - 451 2018.05

    ISSN  14397595

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    © 2017 Japan College of Rheumatology. Objectives: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. Methods: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28–erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. Results: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. Conclusion: A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.

  • Persistent fever and destructive arthritis caused by dialysis-related amyloidosis

    Matsumoto K., Kikuchi J., Kaneko Y., Yasuoka H., Suzuki K., Tokuyama H., Kameyama K., Yamaoka K., Takeuchi T.

    Medicine (United States) (Medicine (United States))  97 ( 1 )  2018.01

    ISSN  00257974

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    Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. Rationale: Dialysis-related amyloidosis (DRA) can present rheumatic manifestations in patients on long-term hemodialysis. Typical articular symptoms with DRA involve carpal-tunnel syndrome, effusion in large joints, spondyloarthropathy, or cystic bone lesions, which are usually with non-inflammatory processes. Patient concerns: A 64-year-old man on hemodialysis for >30 years was admitted because of intermittent fever, polyarthritis, and elevated serum C-reactive protein (CRP) level, which was continuous for 2 years. Several antibiotics were ineffective for 3 months before his admission. On physical examination, joint swelling was observed at bilateral wrists, knees, ankles, and hip joints. Laboratory tests revealed elevation of serum inflammatory markers and β2-microglobulin (β2-MG). Synovial fluid showed predominant infiltration of polymorphonuclear leukocytes and the increase of β2-MG level. Diagnosis: Significant deposition of β2-MG with inflammatory cell infiltration was found in biopsied samples from synovium, skin, and ileum. Interventions: We decided to switch to the hemodialysis column with membrane that can effectively absorb β2-MG in circulation. Outcomes: The relief of symptoms and a decrease of CRP level by changing the membrane lead to the final diagnosis of DRA. Lessons: Our case demonstrates that DRA arthropathy can be inflammatory and destructive, and also develop systemic inflammatory signs and symptoms. In such cases, aggressive absorption of β2-MG in circulation might help the amelioration of symptoms.

  • Methotrexate-associated Intravascular Large B-cell Lymphoma in a Patient with Rheumatoid Arthritis

    Kikuchi, J., Kaneko, Y., Kasahara, H., Emoto, K., Kubo, A., Okamoto, S. and Takeuchi, T.

    Intern Med 55 ( 12 ) 1661 - 5 2016

    ISSN  1349-7235

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    Intravascular large B-cell lymphoma (IVLBCL) is a rare and clinically aggressive lymphoma with an unfavorable prognosis. We report the case of a 50-year-old woman who was diagnosed with IVLBCL during treatment with methotrexate (MTX) and biologic agents for rheumatoid arthritis. The symptoms showed partial improvement only after the cessation of both treatments. She subsequently received chemotherapy and achieved a complete remission and has remained free of recurrence for 2 years without any further treatment. We herein describe a rare case of IVLBCL which presented with the features of an MTX-associated lymphoproliferative disorder.

  • Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with clinical response

    Kikuchi, J., Hashizume, M., Kaneko, Y., Yoshimoto, K., Nishina, N. and Takeuchi, T.

    Arthritis Res Ther 17   10 2015

    ISSN  1478-6362

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    INTRODUCTION: Tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, is clinically effective against rheumatoid arthritis (RA), and several reports have indicated how TCZ influences a number of mechanisms underlying RA pathogenesis. However, it is still unclear whether TCZ affects inflammatory cells in peripheral blood and whether any such changes are associated with clinical response. We evaluated associations between proportions of subsets of peripheral immune cells and clinical response in patients with RA treated with TCZ. METHODS: Thirty-nine consecutive patients with RA who started to receive TCZ as their first biologic between March 2010 and April 2012 were enrolled. The proportions of several subsets of peripheral cells with their levels of expression of differentiation markers, activation markers and costimulatory molecules were measured sequentially from baseline to week 52 by flow cytometry analysis. RESULTS: Clinical Disease Activity Index (CDAI) remission was achieved in 53.8% of patients at week 52 of TCZ therapy. The proportions of CD4(+)CD25(+)CD127(low) regulatory T cells (Treg) and HLA-DR(+) activated Treg cells significantly increased with TCZ therapy (P < 0.001 and P < 0.001, respectively), whereas proportions of CD3(+)CD4(+)CXCR3(-)CCR6(+)CD161(+) T helper 17 cells did not change over the 52 weeks. The proportions of CD20(+)CD27(+) memory B cells, HLA-DR(+)CD14(+) and CD69(+)CD14(+) activated monocytes, and CD16(+)CD14(+) monocytes significantly decreased (P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively). Among them, only the change in Treg cells was inversely correlated with the change in CDAI score (rho = -0.40, P = 0.011). The most dynamic increase in Treg cells was observed in the CDAI remission group (P < 0.001). CONCLUSION: This study demonstrates that TCZ affected proportions of circulating immune cells in patients with RA. The proportion of Treg cells among CD4(+) cells correlated well with clinical response.

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 全身性エリテマトーデスのマルチオミックス解析による新規バイオマーカーの開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • Optimization of the treatment of systemic lupus erythematosus by immunological classifications


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Principal investigator

Awards 【 Display / hide

  • 優秀ポスター賞

    2012.09, 日本臨床免疫学会, IL-6阻害剤とTNF阻害剤はRA患者末梢血中のCD4+CD45RO+CCR6+CD161+細胞に異なった影響を及ぼす


Courses Taught 【 Display / hide










Memberships in Academic Societies 【 Display / hide

  • 日本内科学会

  • 日本リウマチ学会

  • 日本臨床免疫学会