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  2. Naotake Tsuboi

Naotake Tsuboi

  (坪井 直毅)

Profile Information

Affiliation
Graduate School of Medicine Program in Integrated Medicine Internal Medicine, Fujita Health University
Degree
Doctor of Philosophy for Medical Science(Nagoya University)
J-GLOBAL ID
201001034860762065
researchmap Member ID
1000314029

Research History

 16
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Education

 2

Committee Memberships

 1

Awards

 1

Papers

 152
  • Masaya Hirayama, Yukako Ohyama, Yudai Tsuji, Tetsuro Enomoto, Midori Hasegawa, Naotake Tsuboi, Jan Novak, Kazuo Takahashi
    Clinical and experimental nephrology, Apr 7, 2025  
    BACKGROUND: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis. Elevation in the blood levels of aberrantly glycosylated IgA1 is a crucial initial step in IgAN pathogenesis. Here, we aimed to determine the longitudinal changes in the serum levels of IgA1 O- and N-glycoforms in patients with IgAN receiving different treatments. METHODS: We enrolled Japanese patients diagnosed with primary IgAN: 10 patients who underwent tonsillectomy and corticosteroid therapy (T-CST), 7 who received corticosteroid therapy (CST), 8 who received conservative therapy (CO), and 5 with other renal diseases who received corticosteroid therapy (ORD) as disease controls. IgA was purified from patient sera collected at diagnosis and post-treatment. After sample preparation, O-glycoforms of the hinge region (HR) and N-glycoforms of the fragment crystallizable region were analyzed using high-resolution mass spectrometry (MS). RESULTS: The MS analysis of O-glycoforms of IgA1 showed that the relative abundance of IgA1 with 3GalNAc3Gal, which we previously identified as a characteristic IgA1 O-glycoform in IgAN, decreased post-treatment only in the T-CST group (P = 0.0195). Regarding N-glycoforms, the relative abundance of fucosylated N-glycan at asparagine (Asn)340 increased in the IgAN group compared with that in the ORD group (P = 0.0189) and decreased post-treatment only in the T-CST group (P = 0.0195). CONCLUSION: The MS analysis of O- and N-glycoforms of IgA1 revealed substantial changes in their abundance in the T-CST group but not in the CST, CO, and ORD groups. Our study provides new insights into how specific treatments alter the IgA1 glycoform abundance.
  • Masanori Nakanishi, Tomohiro Mizuno, Shinya Sakai, Daiki Hira, Takenao Koseki, Takeshi Matsubara, Hideki Yokoi, Motoko Yanagita, Tomohiro Terada, Shigeki Yamada, Naotake Tsuboi
    Clinical Drug Investigation, Mar 13, 2025  
  • Yasuhiro Katsumata, Ken-Ei Sada, Tomohiro Kameda, Hiroaki Dobashi, Shinya Kaname, Naotake Tsuboi, Yoshinori Matsumoto, Koichi Amano, Naoto Tamura, Masayoshi Harigai
    Immunological medicine, 48(1) 47-57, Mar, 2025  
    We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.
  • Yukinori Aimiya, Sho Hasegawa, Mikio Sakakibara, Midori Hasegawa, Naotake Tsuboi, Naoki Nakagawa, Shigeki Yamada
    Journal of clinical medicine, 14(3), Jan 21, 2025  
    Background: Progression of chronic kidney disease (CKD) increases the risk of complications such as cardiovascular disease; however, knowledge regarding renal function in the general population is low. We aimed to determine factors necessitating CKD education in the general population. Methods: Participants for a health promotion seminar were recruited via the Sugiura Memorial Foundation website and Sugi Pharmacy stores. Those who agreed to participate in the seminar were included in the questionnaire survey after a health seminar. Results: Out of 1548 participants, 1050 answered all questionnaire items, resulting in a valid response rate of 67.83%. Multivariable analysis revealed that sex (OR = 0.611), pharmacy consultations (OR = 0.661), receiving a blood test within 1 year (OR = 0.268), awareness of blood pressure (OR = 0.038), and knowledge of blood glucose level (OR = 0.099) were factors for unawareness of renal function. Conclusions: This study suggests that female individuals unaware of their blood pressure or glucose levels, those who have not had a blood test within 1 year, and those who have not sought health consultations need education on renal function.
  • Shun Minatoguchi, Hiroki Hayashi, Ryosuke Umeda, Shigehisa Koide, Midori Hasegawa, Naotake Tsuboi
    CEN CASE REPORTS, 13(5) 419-424, Oct, 2024  
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Misc.

 165

Books and Other Publications

 23
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Presentations

 12
  • 伊藤 辰将, 辰川 英樹, 梅田 良祐, 横江 優貴, 高橋 和男, 湯澤 由紀夫, 人見 清隆, 坪井 直毅
    日本腎臓学会誌, Jun, 2021, (一社)日本腎臓学会
  • 坪井 直毅, 横江 優貴, 北川 章充, 伊藤 辰将, 遠藤 信英, 丸山 彰一
    腎臓内科, Jun, 2021, (有)科学評論社
  • 細江 眞生, 森 万佑子, 鈴木 むつみ, 山田 幸恵, 新 典雄, 加藤 政雄, 大高 洋平, 長谷川 みどり, 坪井 直毅, 中井 滋
    日本透析医学会雑誌, May, 2021, (一社)日本透析医学会
  • 吉田 浩之, 湯澤 由紀夫, 長谷川 みどり, 稲熊 大城, 坪井 直毅, 林 宏樹, 小出 滋久, 大山 翔也, 多賀谷 知輝, 伊藤 辰将, 成宮 利幸, 磯貝 理恵子, 古田 弘貴, 堀内 雅人
    腎と透析, Aug, 2020, (株)東京医学社
  • Yuki Yokoe, Naotake Tsuboi, Takahiro Imaizumi, Akimitsu Kitagawa, Munetoshi Karasawa, Takaya Ozeki, Nobuhide Endo, Yuriko Sawa, Sawako Kato, Takayuki Katsuno, Shoichi Maruyama, Kunihiro Yamagata, Joichi Usui, Michio Nagata, Ken-Ei Sada, Hitoshi Sugiyama, Koichi Amano, Yoshihiro Arimura, Tatsuya Atsumi, Yukio Yuzawa, Hiroaki Dobashi, Yoshinari Takasaki, Masayoshi Harigai, Hitoshi Hasegawa, Hirofumi Makino, Seiichi Matsuo
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jul 8, 2020
    BACKGROUND: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. METHODS: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. RESULTS: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. CONCLUSIONS: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.
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Teaching Experience

 2

Professional Memberships

 5

Research Projects

 18
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