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

干燥综合征患者早期恶性淋巴瘤的研究

• 批准号: 08670541
• 负责人: SUGAI Susumu
• 金额: $ 1.34万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670541/
• 关键词: Sjogren'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

(1)Studies on the monoclonality of Ig VL genesSF18/2 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 genesThe 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

（1）IG VL基因的单克隆性研究来源于干燥综合征（SS）患者的SF 18/2独特型在SS患者的血清和外周血淋巴细胞表面膜上频繁检测到（1）。我们证明了这种SF 18/2独特型是VK III亚组成员Vg生殖系基因的产物（2）。然后，我们研究了从SS患者外周血白细胞DNA样品中的Vg基因重排。87%的SS患者存在274 kb的重排片段。通过对这些片段进行测序，显示其中一个片段与Vg种系基因具有98.5%的同源性，另一个片段与CDR 3区的8个置换突变具有95.8%的同源性（3）。认为Vg生殖系基因的高频率重排是引发SS患者淋巴细胞增殖的因素之一。（2）IG VH-CDR 3基因的单克隆性研究 ...更多信息 用合适的引物对50例SS患者的唇活检组织和IgVH-CDR 3区进行双链PCR扩增，在50例SS患者的唇活检组织中，有7例出现单克隆或寡克隆条带[4]。6例SS患者的大唾液腺出现结节。这些结节已被手术切除，病理证实为良性。6份样品中有4份显示单克隆条带。对这些条带进行亚克隆和测序，结果显示2个来自不同患者的共同DNA序列。这些序列与恶性淋巴瘤或骨髓瘤患者中报道的那些基因具有密切的同源性（5）。在2例患者的4份泪腺样本中，有3份样本显示单克隆条带（6）。这些样本的DNA序列与唾液腺中发现的DNA序列不同。这些数据表明，B细胞单克隆增殖发生在小或大唾液腺和泪腺的慢性炎症部位，并在SS患者中发展为恶性。少

项目成果

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)

Susumu Sugai、Takeshi Sasaki等人：“易于理解的内科（自身免疫性疾病/自身抗体的发病机制）”Bunkodo Co., Ltd.（出版中），（1998年）

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)

M.Hiraoka、S.Sugai 等人：“干燥综合征泪腺淋巴增殖性疾病中 CD44 剪接变体的增强表达”Jpn J Ophamol。

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)

Sugai, S.、Shimizu, S.、Tachibana, J. 等人：“干燥综合征患者血清中的单克隆蛋白和淋巴瘤细胞中类风湿因子独特型的发生率很高。”

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)

Sugai S、Masaki T、Shimizu S 等人：“干燥综合征患者外周血 DNA 中的 V kappa 种系基因重排。”

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)

Sugai S、Kato S、Takeshita S：“六名干燥综合征患者主要唾液腺组织中 B 细胞群 IGVHCDR3 的分析。”