1996 Fiscal Year Final Research Report Summary
Development of a novel diagnostic tool using recombinant pemphigus antigens with the proper native conformation.
| Project/Area Number |
07557064
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
NISHIKAWA Takeji Keio Univ.Sch.Med., Assist.Prof., 医学部・皮膚科, 教授 (50051579)
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| Co-Investigator(Kenkyū-buntansha) |
OHATA Yoshiyuki Keio Univ.Sch.Med., Instructor, 医学部, 助手 (30213838)
GAMOU Shinobu Keio Univ.Sch.Med., Assist.Prof., 医学部・分子生物学, 講師 (90122308)
SHIMIZU Nobuyoshi Keio Univ.Sch.Med., Professor, 医学部・分子生物学, 教授 (50162706)
AMAGAI Masayuki Keio Univ.Sch.Med., Professor, 医学部, 講師 (90212563)
HASHIMOTO Takashi Kurume Univ.Sch.Med., Professor, 医学部・皮膚科, 教授 (20129597)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Autoimmune Disease / Pemphigus / Desmosome / Desmoglein / Diagnostic tool / ELISA / Recombinant Protein / Cadherin |
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| Research Abstract |
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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