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Investigation into the roles of autoantibodies in the pathogenesis of central nervous system lupus erythematosus.

自身抗体在中枢神经系统红斑狼疮发病机制中作用的研究。

基本信息

批准号：
12670438
负责人：
HIROHATA Shunsei
金额：
$ 2.18万
依托单位：
Teikyo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

We examined the presence of the epitope recognized by antiribosomal P protein antibody (anti-P) on the cell surface of human immunocompetent cells in order to delineate its role in the pathogenesis of CNS lupus. Highly purified CD4+ and GD8+ T cells, monocytes, and B cells from normal healthy individuals were reacted with affinity-purified IgG anti-P, and were stained with FITC-conjugated F(ab')_2, fragment goat anti-human IgG, followed by analysis on flow cytometry with gating for viable cells by propidium iodide staining. The presence of an epitope that is antigenically related to the earboxyl-terminal 22-amino-acid sequence of ribosomal P protein was not demonstrated on the surface offreshCD4+ and CD8+ T cells, monocytes, or fresh B cells. However, the expression of the ribosomal P epitope was induced on CD4+ and CD8+ T cells after activation with immobilized anti-CD3 and on monocytes after 24h incubation with on without IFN-γ, whereas the epitope was not expressed on activated B cells. These results indicate that anti-P is an antilymphocyte' antibody, which reacts with activated T cells and monocytes but not with resting T cells, monocytes or B cells, suggesting possible direct effects of anti-P on the immune dysregulation in systemic lupus erythematosus. We could not detect significant elevation of anti-glutamate receptor antibody in cerebrospinal fluid from patients with lupus psychosis, indicating that recognized by anti-neuronal antibody.

我们检测了抗核糖体P蛋白抗体(anti-P)识别的表位在人类免疫活性细胞表面的存在，以探讨其在中枢神经系统狼疮发病机制中的作用。取正常人外周血中高纯度的CD4+、GD8+T细胞、单核细胞和B细胞，与亲和纯化的Ig G抗P反应，用FITC标记的F(ab‘)2、片段羊抗人Ig G进行染色，然后进行流式细胞术分析，并用碘化丙啶染色门控检测活细胞。在CD_4~+和CD_8~+T细胞、单核细胞或新鲜B细胞表面未发现与核糖体P蛋白耳端22位氨基酸序列相关的抗原表位。经固定化抗CD_3激活后的CD_4~+、CD_8~+T细胞和未加干扰素-γ的单核细胞24小时后均可表达核糖体P表位，而活化的B细胞则不表达核糖体P表位。这些结果表明，抗P抗体是一种抗淋巴细胞抗体，可与活化的T细胞和单核细胞反应，而不与静止的T细胞、单核细胞或B细胞反应，提示抗P抗体可能在系统性红斑狼疮免疫失调中起直接作用。在狼疮精神病患者脑脊液中未检测到抗谷氨酸受体抗体的显著升高，提示其被抗神经元抗体所识别。