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The Studies on the Early Phase of Mlignant Lymphoma in Patients with Sjogren's Syndrome

Research Project

Project/Area Number 08670541
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKanazawa Medical University

Principal Investigator

SUGAI Susumu  Clinical Science, Medical Research Institute, Kanazawa Medical University Professor, 付置研究所, 教授 (20064537)

Co-Investigator(Kenkyū-buntansha) TAKESHITA Shouichi  Hematology and Immunology, Internal Medicine, KanazawaMedical University Assitan, 医学部, 助手 (50247441)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsSjogren's syndrome / Lymphoproliferation / Malignant lymphoma / Idiotype / Vg gene / IgVH-CDR3 / PCR / Lachrymal glands / IgVH遺伝子 / 唾液腺 / リウマトイド因子
Research Abstract

(1)Studies on the monoclonality of Ig VL genes
SF18/2 idiotype derived from a patient with Sjogren's syndrome (SS) was frequently detected in sera and on the surface membrane of the peripheral blood lymphocytes from SS patients (1). We proved that this SF18/2 idiotype was a product of the Vg germline gene which is a member of the VK III subgroup (2). Then, we studied the rearrangement of the Vg gene in DNA samples from the peripheral blood leukocytes from SS patients. The rearranged 274kb fragments were detected in 87% of SS patients. By sequencing these fragments, it was shown that one has the 98.5% homology to the Vg germline gene and another has the 95.8% homology with 8 replacement mutations in the CDR3 region (3). It was considered that the high frequency of the rearrangement of the Vg germline gene is one of the factors to trigger the development of lymphoproliferation in SS patients.
(2)Studies on the monoclonality of Ig VH-CDR3 genes
The DNA samples were prepared from the lip biop … More sy specimens of 50 SS patients and the IgVH-CDR3 regions were amplified by seminested PCR using appropriate primers.
Among 50 samples of the lip biopsy from SS patients, 7 showed monoclonal or oligoclonal bands (4). Six patients with SS developed nodules in their major salivary glands. These nodules had been resected surgically and were proved to be pathologically benign. Four out of 6 samples showed monoclonal bands. The subcloning and sequencing of these bands showed 2 common DNA sequences from different patients. These sequences had the close homology to those genes reported in patients with malignant lymphoma or myeloma (5). Among 4 samples from lachrymal glands from 2 patients who showed swollen lachrymal glands, 3 showed monoclonal bands (6). The DNA sequences of these samples were different from those found in salivary glands. These data indicate that B cell monoclonal proliferation occurs in the chronic inflammation sites in minor or major salivary glands and lachrymal glands and develops to be malignant in patients with SS. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] S.Kumagai, S.Sugai et al: "Association of a New Allele of the TAP2 Gene,TAP2^* Bky(Val^<577>),with Susceptibility to Sjogren's Syndrome" ARTHRITIS & RHEUMATISM. 40. 1685-1692 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Hiraoka, S.Sugai et al: "Augmented Expression of CD44 Splice Variants in lymphoproliferative Disorder of the Lacrimal Gland in Sjogren's Syndrome" Jpn J Ophthalmol. 41. 312-318 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 崔 国恵, 菅井 進, 他: "10年以上経過を観察したシェ-グレン症候群43例の解析" リウマチ. 37. 770-780 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 菅井 進: "Sjogren症候群とリンパ増殖性病変" Mol.Med.34. 156-163 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 菅井 進, 崔 国恵, 他: "シェ-グレン症候群の口唇小唾液腺生検組織に関する厚生省診断基準の検討" 厚生省特定疾患免疫疾患調査研究班報告書. 283-297 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 正木 康夫, 菅井 進, 他: "Combinatorial Antibody Libraryによるヒト型単クローン性抗核抗体の作成" 厚生省特定疾患免疫疾患調査研究班報告書. 292-297 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 菅井 進 他: "今日の治療指針 1998版" (株)医学書院, 2 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 菅井 進, 佐々木 毅, 他: "分かりやすい内科学(自己免疫疾患の発生機序/自己抗体)" (株)文光堂(in press), (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugai, S., Shimizu, S., Tachibana, J., et al: "A high incidence of rheumatoid factor idiotypes in monoclonal proteins in the serum and in lymphoma cells in patients with Sjogren's syndrome." J.Autoimm.2. 471-476 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugai, S., Saito, I., Masaki, Y., et al.: "Rearrangement of the rheumatoid factor-related germline gene Vg and bcl-2 expression in lymphoproliferative disorders in patients with Sjogren's syndrome." Clin.Immunol.Immunopathol.72. 181-186 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugai S,Masaki T,Shimizu S et al: "V kappa germline gene rearrangement in the perioheral blood DNA in patients with Sjogren's syndrome." Annual Reports of Autoimmune Deseases Group of Ministry of Health and Welfare. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Jordan R,Masaki Y,Takeshita S,Speight P.M,Sugai S: "High patients. prevelence of B-cell monoclonality in labial gland bioposies of Japanese Sjogren's syndrome" Intern J Hematol. 64. 47-52 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugai S,Kato S,Takeshita S: "The analysis of IGVHCDR3 of B-cell populations in the major salivary gland tissues in six patients with Sjogren's syndrome." Annual Reports of Autoimmune Deseases Group of Ministry of Health and Welfare. 49-51 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugai S,Kato S,Takeshita S: "The analysis of IGVHCDR3 of B-cell populations in the swollen lachrymal gland tissues in two patients with Sjogren's syndrome." Annual Reports of Autoimmune Deseases Group of Ministry of Health and Welfare. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Kumagai.,S.Sugai et al: "Association of a New Allele of the TAP2 Gene,TAP2^★Bky(Val^<577>),with Susceptibility to Sjogren's Syndrome" ARTHRITIS & RHEUMATISM. 40. 1685-1692 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Hiraoka.,S.Sugai et al: "Augmented Expression of CD44 Splice Variants in lymphoproliferative Disorder of the Lacrimal Gland in Sjogren's Syndrome" Jpn J Ophthalmol. 41. 312-318 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 崔 国恵、菅井 進、他: "10年以上経過を観察したシェ-グレン症候群43例の解析" リウマチ. 37. 770-780 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 菅井 進: "Sjogren症候群とリンパ増殖性病変" Mol. Med.34. 156-163 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 菅井 進、崔 国恵、他: "シェ-グレン症候群の口唇小唾液腺生検組織に関する厚生省診断基準の検討" 厚生省特定疾患免疫疾患調査研究班報告書. 283-291 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 正木康史、菅井 進、他: "Combinatorial Antibody Libraryによるヒト型単クローン性抗核抗体の作成" 厚生省特定疾患免疫疾患調査研究班報告書. 292-297 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 菅井 進 他: "今日の治療指針 1998版" (株)医学書院, 2 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 菅井 進、佐々木 毅、他: "分かりやすい内科学(自己免疫疾患の発生機序/自己抗体)" (株)文光堂(in press), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] R.C.K.Jordan,.S.Sugai,.et al: "High prevalence of B-cell monoclonality in labial gland biopsies of Japanese Sjogren's syndrome patients." Inter. Journal of Hematology.

    • Related Report
      1996 Annual Research Report
  • [Publications] 菅井進: "Sjogren症候群とリンパ増殖性病変" Molecular Medicine.

    • Related Report
      1996 Annual Research Report
  • [Publications] 陳听、菅井進、他: "Sjogren症候群患者におけるリウマトイド因子イディオタイプの研究" 日本臨床免疫学会会誌.

    • Related Report
      1996 Annual Research Report
  • [Publications] 西成田真、菅井進他: "多発性骨髄腫(IgA-k)の経過中IgAリウマトイド因子(RF)が出現した1例" 日本臨床免疫学会会誌.

    • Related Report
      1996 Annual Research Report
  • [Publications] 菅井進: "自己免疫疾患における悪性腫瘍の発症" 日本臨床免疫学会会誌.

    • Related Report
      1996 Annual Research Report
  • [Publications] 菅井進: "シェ-グレン症候群" リウマチ科.

    • Related Report
      1996 Annual Research Report
  • [Publications] 南部静洋、大谷信夫、菅井進: "間質性肺炎の病態と治療(シェ-グレン症候群における肺病変)" 診療新社,

    • Related Report
      1996 Annual Research Report
  • [Publications] 中井利昭他,菅井進: "症候・異常値診断マニュアル(リウマトイド因子(RF))" 中外医学社,

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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