Development of a novel diagnostic tool using recombinant pemphigus antigens with the proper native conformation.
Development of a novel diagnostic tool using recombinant pemphigus antigens with the proper native conformation.
批准号:
07557064
负责人:
NISHIKAWA Takeji
金额:
$7.81万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (A)
财政年份:
1995
资助国家:
日本
项目状态:
已结题
起止时间:
1995 至 1996
中文摘要
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英文摘要
Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune skin diseases caused by autoantibodies against two different members of the desmoglein family of adhesion proteins, desmoglein (Dsg) 3 and Dsg 1, respectively. Routine immunofluorescence testing of both the skin and serum from patients with both forms of pemphigus is unable to distinguish between these two diseases since both have IgG antibodies directed against keratinocyte cell surfaces. It is important, however, to distinguish between these two diseases for determining treatment plans and prognosis, and potentially for following disease activity. In this study, recombinant Dsg1 and Dsg3, produced as secreted proteins by baculovirus expression, have been utilized to develop sensitive and specific ELISAs for the diagnosis of patients with pemphigus and for the specific characterization of their auto antibodies. 46 of 49 (94%) patients with pemphigus vulgaris (PV) were positive in the DSG3 ELISA,compared to 0 of 46 (0% … More ) patients with pemphigus foliaceus (PF). In contrast, 44 of 46 (96%) of patients with PF were positive in the Dsg1 ELISA compared to only 26 of 49 (53%) patients with PV.Both the Dsg1 and Dsg3 ELISAs were more specific and sensitive than conventional immunofluorescence (Routine DIF positive : PV=86%, PF=89%). Correlation of disease activity with ELISA reactivity revealed a correlation in disease activity and ELISA scores in 5 of 6 patients with PV and all patients with PF.Further analysis of the anti-Dsg1 antibodies found in the serum of some patients with PV revealed no evidence of cross-reactivity between anti-Dsg1 and anti-Dsg3 antibodies. Anti-Dsg1 antibodies were found most frequently and in higher titer in PV patients with significant skin involvement than those PV patients with predominantly oral mucosal lesions. Utilization of Dsg1 and Dsg3 ELISAs provides a sensitive and highly specific assay for the diagnosis of patients with PF and PV,the prospective correlation of the disease activity with serum antibody levels, and for development of a better understanding of fundamental immunopathological mechanisms of pemphigus. Less
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Murakami H,Amagai M,Higashiyama M,Hashimoto K,Chorzelski TP,Bhogal BS,Black MM,Zillikens D,Nishikawa T,Hashimoto T: "Analysis of antigens recognized by autoantibodies in herpes gestationis:Usefulness of fmmunoblotting using a fusion protein representing a
Murakami H、Amagai M、Higashiyama M、Hashimoto K、Chorzelski TP、Bhogal BS、Black MM、Zillikens D、Nishikawa T、Hashimoto T:“妊娠疱疹中自身抗体识别的抗原分析:使用代表 a 的融合蛋白进行免疫印迹的有用性
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Amagai M,Ishii K,Takayanagi A,Nishikawa T,Shimizu N: "Transport to endoplasmic reticulum by signal peptide,but not prote olytic processing,is required for formation of conformational epitopes of pemphigus velgaris angigen (Dsg 3)." J Invest Dermatol. 107.
Amagai M、Ishii K、Takayanagi A、Nishikawa T、Shimizu N:“通过信号肽转运至内质网,而不是蛋白水解加工,是形成天疱疮血管生成物构象表位 (Dsg 3) 所必需的。”
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Shimizu K,Hashimoto T,Wang N,Watanabe K,Ohata Y,Kikuchi A,Amagai M,Nishikawa T: "A case of herpetiform pemphigus associated with autoimmune hemolytic anemia:detection of autoantibodies against mult epidermal antigens." Dermatology. 192. 179-182 (1996)
Shimizu K、Hashimoto T、Wang N、Watanabe K、Ohata Y、Kikuchi A、Amagai M、Nishikawa T:“与自身免疫性溶血性贫血相关的疱疹样天疱疮一例:针对多种表皮抗原的自身抗体的检测。”
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Amagai M: "Advances in Dermatology" Mosby Year Book, 34 (1996)
Amagai M:《皮肤病学进展》莫斯比年鉴,34 (1996)
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Vilela,M.J.: "A simple epithelial cell line (MDCK) shows heterogeneity of desmoglein isoforms, one resembling pemphigus vulgaris antigen." Journal of Cell Science. 108. 1743-1750 (1995)
Vilela,M.J.:“一种简单的上皮细胞系 (MDCK) 显示桥粒芯糖蛋白异构体的异质性,其中一种类似于寻常型天疱疮抗原。”
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共 27 条
Real-time imaging analysis of cell adhesion molecules of epidermal keratinocytes
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批准号:14370262
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.58万
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财政年份:2002
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负责人:NISHIKAWA Takeji
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依托单位:
Basic studies for development of disease-specific therapeutic strategies against autoimmune diseases
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批准号:12470181
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$10.37万
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财政年份:2000
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负责人:NISHIKAWA Takeji
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依托单位:
Evaluation of immune suppressive therapy using autoimmune model mouse
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批准号:12557072
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.45万
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财政年份:2000
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负责人:NISHIKAWA Takeji
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依托单位:
Development of novel mouse model for autoimmune diseases using autoantigen knockout mice
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批准号:10470189
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$9.66万
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财政年份:1998
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负责人:NISHIKAWA Takeji
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依托单位:
Elucidation of Pathogenetic Mechanisms of Severe Ichthyoses and Establishment of New Method for the Diagnosis and Prenatal Disease Detection
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批准号:10557082
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.77万
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财政年份:1998
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负责人:NISHIKAWA Takeji
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依托单位:
Development of novel therapy against bullous diseases
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批准号:10044318
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项目类别:Grant-in-Aid for Scientific Research (B).
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资助金额:$5.44万
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财政年份:1998
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负责人:NISHIKAWA Takeji
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依托单位:
Clarification of pathogenesis in pemphigus : Establishment of new techniques for diagnosis.
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批准号:05404036
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项目类别:Grant-in-Aid for General Scientific Research (A)
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资助金额:$17.15万
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财政年份:1993
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负责人:NISHIKAWA Takeji
-
依托单位:
Basic studies for the pathogenesis and diagnosis of the autoimmune bullous diseases
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批准号:05044186
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项目类别:Grant-in-Aid for international Scientific Research
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资助金额:$3.52万
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财政年份:1993
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负责人:NISHIKAWA Takeji
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依托单位:
Establishment of prenatal diagnosis of epidermolysis bullosa in Japan
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批准号:04557045
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项目类别:Grant-in-Aid for Developmental Scientific Research (B)
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资助金额:$5.57万
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财政年份:1992
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负责人:NISHIKAWA Takeji
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依托单位:
Application of up-to date immunoelectron microscopy for the study of pathogenesis of skin blistering disease.
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批准号:03454275
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.16万
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财政年份:1991
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负责人:NISHIKAWA Takeji
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依托单位:
Detection of antigen epitope for bullous pemphigois antigenic protein and the development of autoantibody detection using synthetic polypeptide
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批准号:02557045
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项目类别:Grant-in-Aid for Developmental Scientific Research (B)
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资助金额:$6.78万
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财政年份:1990
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负责人:NISHIKAWA Takeji
-
依托单位:
Basic studies for the diagnosis of bullous diseases having pathologic changes at the basement membrane zone
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批准号:02044130
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项目类别:Grant-in-Aid for international Scientific Research
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资助金额:$2.82万
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财政年份:1990
-
负责人:NISHIKAWA Takeji
-
依托单位:
海外基金