Studies on Autoantibody Idiotype (Id) in Autoimmune Diseases and Its Clinical Application

自身免疫性疾病中自身抗体独特型（Id）的研究及其临床应用

• 批准号: 60570305
• 负责人: SUGAI Susumu
• 金额: $ 1.09万
• 依托单位: Kanazawa Medical University, Department of Hematology and Immunolgy Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570305/
• 关键词: Sjogren's syndrome; Rheumatoid factor; Cross-reactive idiotype; Monoclonal anti-idiotypic antibody; Cell surface membrane idiotype; B細胞分化

It is important to study autoantibody idiotype (Id) to clarify the mechanism of autoantibody production and suppression. Rheumatoid factor (RF) is a most common autoantibody seen in many autoimmune diseases. We produced monoclonal anti-Id antisera (mA-Id) by the cell hybridization technique against 3 monoclonal RFs (IgM-K, IgA-L and IgA-K) in patients with Sjogren's syndrome (SS) and one monoclonal RF (IgM-K) in a patient with Waldenstrom's macroglobulinemia. These mA-Id were site-specific antibodies against RFs. The Id determinant was studied by Western blot analysis and identified on the kappa chain (2 IgM-K), mu, kappa and alpha (?) chain (IgA-L) and mu and alpha-kappa chain (IgA-K), respectively. One mA-Id against IgA-K RF detected small nuclear RNPs in the proliferating lymphoid cells. Cross-reactive Id (CRI) was examined among 50 M proteins and 50 sera containing polyclonal RFs by dot and agar gel electrophoresis immunoblot analyses; CRI was found in 40-90% of 7 monoclonal RFs, 10 M proteins and 10 cryoglobulins in SS patients. Some M proteins without RF activity, a few of sera containing polyclonal RFs and even some normal sera showed CRI. These results suggest that there is a RF V gene family or families shared in common in patients and normal persons and these are highly expressed in autoimmune diseases such as SS. Cell surface Id (SmId) and SmIg of peripheral blood lymphocyts (PBL) were examined by the double immunofluorescence method. B cells bearing SmId (0.3-11.8%) were identified in PBL of 4 SS patients with monoclonal RF. B cell differentiation to plasma cells containing cytoplasmic Id was observed in 3 patients by PWM stimulation. These results indicate that monoclonal B cells are pressent in PBL of patients with RF and differentiate to plasma cells in vivo by some stimulations and there might be some controlling mechanism to stimulate or suppress the differentiation of these monoclonal B cells.

研究自身抗体独特型对阐明自身抗体的产生和抑制机制具有重要意义。风湿因子（RF）是一种常见的自身免疫性疾病的自身抗体。我们用细胞杂交技术制备了抗Sjogren综合征（SS）患者3种单克隆RF（IgM-K、IgA-L和IgA-K）和1例Waldenstrom巨球蛋白血症患者1种单克隆RF（IgM-K）的单克隆抗Id抗血清（mA-Id）。这些mA-Id是针对RF的位点特异性抗体。通过Western印迹分析研究了Id决定簇，并在κ链（2 IgM-K）、μ、κ和α（？）链（IgA-L）以及μ和α-κ链（IgA-K）。一个针对IgA-K RF的mA-Id在增殖的淋巴样细胞中检测到小的核RNP。用斑点和琼脂凝胶电泳免疫印迹分析法检测了50个M蛋白和50个含有多克隆RF的血清之间的交叉反应性Id（CRI），在SS患者的7个单克隆RF、10个M蛋白和10个cryocellulins中发现40-90%的CRI。部分无RF活性的M蛋白、少数含有多克隆RF的血清及部分正常人血清显示CRI。这些结果表明，在患者和正常人中存在一个或多个共有的RF V基因家族，并且这些基因在自身免疫性疾病如SS中高度表达。用免疫荧光双标法检测外周血淋巴细胞（PBL）的细胞表面Id（SmId）和SmIg。4例SS患者外周血淋巴细胞中检出SmId（0.3-11.8%）的B细胞。3例患者经PWM刺激后，B细胞向浆细胞分化，浆细胞内含有Id。提示RF患者外周血淋巴细胞中存在单克隆B细胞，并在一定的刺激下向浆细胞分化，可能存在某种调控机制来刺激或抑制单克隆B细胞的分化。

项目成果

Shiro Shimizu: "Monoclonal anti-idiotypic antibodies against monoclonal rheumatoid factors derived from patients with Sjogren's syndrome." Scand. J. Rheumatol.(1986)

Shiro Shimizu：“针对来自干燥综合征患者的单克隆类风湿因子的单克隆抗独特型抗体。”

Talal N;Moutsopoulos HM;Kassan S,eds.Sugai S: "Sjogren's Syndrome:Clinical and Immunological Aspects," Lymphoproliferative disorders in Japanese patients with Sjogren's syndrome., 18 (1987)

Talal N；Moutsopoulos HM；Kassan S，eds.Sugai S：“干燥综合征：临床和免疫学方面”，日本干燥综合征患者的淋巴增殖性疾病。，18 (1987)

Susumu Sugai: "Lymphoproliferative disorders in Japanese patients with Sjogren's syndrome." Scand. J. Rheumatol.(1986)

Susumu Sugai：“日本干燥综合征患者的淋巴增殖性疾病。”

Shimizu S: Scand.J.Rheumatol.(1986)

清水 S：Scand.J.Rheumatol.(1986)

Susumu Sugai: "M protein idiotype in patients with monoclonal gammopathy." Acta Haematol. Jpn.49. 1749-1756 (1986)

Susumu Sugai：“单克隆丙种球蛋白病患者的 M 蛋白独特型。”