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1991 Fiscal Year Final Research Report Summary

Development of Intradermal Sensitization Therapy to Ra Patients Using Oncofetal Carbohydrate Membrane Structure

Research Project

Project/Area Number 01870065
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionOsaka University

Principal Investigator

OCHI Takahiro  Osaka University Medical School, Environmental Medicine, Professor, 医学部, 教授 (80112035)

Co-Investigator(Kenkyū-buntansha) KIMURA Tomoatu  Osaka University Medical School, Orthopedic Surgery, Assistant Professor, 医学部, 助手 (80167379)
ONO Keiro  Osaka University Medical School, Orthopedic Surgery, Professor, 医学部, 教授 (70028330)
Project Period (FY) 1992 – 1994
KeywordsRA Patient / Myeloid Cell / Oncofetal Markers / Carbohydrate Structure / Sensitization Therapy / Di-fucosylated Type 2 Chain / Glycoprotein Derivative (TCA)
Research Abstract

Di-and trifticosyl N-acetyllactosamine structures have been found as oncofetal markers defined by monoclonal antibody FH4 (J Biol Chem, 1984). Recently these membrance structures were identified in the abnormal myeloid cells found in the involved epiphyseal bone marrow of severe RA patients (Ochi et al, 1988).
Recently, sialyl Lewis X was found to mediate the cell adhesion by ELAM-1 (Phillips et al, 1990). Thus, carbohydrate membrance structure was found to be important in relation to the patholgy of RA.
We have tried the sensitization therapy with some carbohydrate structures to normalize the pathologic lesions in RA patients. As antigens, we used mono-, and di-fticosylated type 2 chain (mono-LeX, and di-Lex ; 500ng for each injection) bolind to liposome, and a high molecular weight glycoprotein derived from KATOIll cells (TCA ; provided by JIMBO ; 50 or 2 ng for one injection). One sensitization schedule was intradermal injection at day 1 and 2 with following 12 days interval (one cour … More se term).
The first study was the investigation of the effect of i. d. injection of carbohydrate materials on the myeloid cell population present in epiphyseal bone marrow adjacent to a joint with active severe RA. Among RA patients with those abnormal cells, epiphyseal bone marrow cells were re-examined after 2 or more course terms of i. d. injections (1 to 4 months ; mean 2.5 months). The ratio of abnormal myeloid cells to whole mononuclear cells was assessed by facs. The mean ratios (N=10) before and after the i. d. injections of di-LeX were 8.32 (SD : 2.54) and 2.04 (SD : 1.81), respectively. The abnormal myeloid cells were, even if temporality, eliminated from the involved epipyseal bone marrow.
The second study was open trials to assessed the effects of materials and dosis. As the effective cases, not only clinical improvements bu't also the normalization of one or more laboratory data (IgM-RF, IgG-RF, CRP, ESR) were needed after 3 or 6 months of treatments. As antigens, di-LeX and TCA were effective both at 3 and 6 months' treatments. However, mono-Le^X showed no significant effect so far. Among the 105 trials with carbohydrate antigens, 15cases (14%) showed adverse effects ; skin eruption (11 cases), stomatitis aphtosa (2 cases) and hairloss (2 cases).
The Incidences of effective cases (among 132 trials) were as below.
Antigens Used Placebo di-LeX mono-LeX 2nd-TCA 50ng-TCA
After 3M 6/27(22%) 20/29(69%) 0/5(0%) 12/24(50%) 29/47(62%)
After 6M 6/25(24%) 17/27(63%) N. D. 14/22(64%) 31/43(72%)
Carbohydrate structures COLild be good materials in treating RA patients. Although the mecanisms are still obscure. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ochi T,Hakomori S,Fujimoto M,et al: "Therapeutic effect of intradermal injections with difucosyl lactosamine on RA patients" Journal Rheumatology.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 越智 隆弘: "RA患者に対する糖鎖抗原による感作療法" Medical Topics Seriesリウマチ'92.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柏木 伸仁,越智 隆弘: "癌由来糖鎖抗原が自己リンパ球混合培養反応に与える影響" リウマチ.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 越智 隆弘,藤本 真弘,岡村 まさ恵,他: "糖鎖抗原" リウマチ. 31. 629-630 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柏木 伸仁,岡村 まさ恵,越智 隆弘: "癌細胞由来糖鎖複合体によるRA患者自己リンパ球混合培養反応の抑制" リウマチ学会. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ochi T,Hakomori S,Shimaoka Y,et al: "A theraprutic effect of sensitization with oncofetal carbohydrate membrane structures on RA patients" 5th World Conference on Clinical Pharmacology and Therapeutics. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ochi T, Hakomori S, Fujimoto M, et al: "Therapeutic effect of intradermal injections with difucosyl lactosamine on RA patients" Journal Rheumatology.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochi T, Hakomori S, Shimaoka Y, et al: "A therapeutic effect of sensitization with oncofetal carbohydrate membrane structures on RA patients" 5th World Conference on Clinical Pharmacology and Therapeutics. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochi T: "Sensitization therapy to RA patients with carbohydrate antigen (in Japanese)" Medical Topics Series Rheumatoid arthritis '92.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kasiwagi N, and Ochi T: "Effect of oncofetal carbohydrate antigen on autologous mixed lynphocyte reaction" Ryumachi (in Japanese).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kasiwagi N, and Ochi T: "Suppressive effect of oncofetal carbohydrate antigen on autologous mixed lymphocyte reaction in RA patients (in Japanese)" Ryumachi (in Japanese).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochi T, Fujimoto M Okamura M et al: "Carbohydrate membrane antigen" Ryumachi (in Japanese). 31. 629-630 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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