Keratinocyte-derived auto antigens involved in systemic autoimmune diseases

角质形成细胞衍生的自身抗原参与系统性自身免疫性疾病

• 批准号: 11470182
• 负责人: FURUKAWA Fukumi
• 金额: $ 6.91万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470182/
• 关键词: anti-SS-A; Ro antibody; ultraviolet light; autoimmune disease; skin; keratinocyte; autoantigen; ループスエリテマトーデス; 表皮細胞; 細胞障害; 培養細胞

1. Anti-SS-A/Ro antibody is bonding to the cell surface of keratinocytes irradiated with ultraviolet B light, which was confirmed by confocal microscopy.2. Autoantibody dependency was confirmed in the cytotoxicity of UVB irradiated keratinocytes of patients plus patients' sera plus mononuclear cells from normal individuals.3. Isolations of nucleosides and autoantigens were performed in the culture supernatants of patients' keratinocytes irradiated with UVB light. Nucleosomes were partially purified and were immunized to MRL/n mice. In these mice, low titer of anti-nucleosome antibody was detected.4. Mononuclear cells from patients with high titer of anti-SS-A/Ro antibody were transferred to SCID mice in order to induce the skin lesions. Our data showed that transferred mice produced slight erythema and hair loss without immunoglobulin and/or complement components depositions at dermoepidermal junction.5. Signal transduction systems are now under investigations.

1.共聚焦显微镜证实抗SS-A/Ro抗体与紫外线B照射的角质形成细胞表面有结合。UVB照射的患者角质形成细胞加患者血清加正常人单个核细胞的细胞毒作用证实具有自身抗体依赖性。在紫外线照射患者角质形成细胞的培养上清液中分离核苷和自身抗原。将部分纯化的核小体免疫MRL/n小鼠。在这些小鼠中，检测到低滴度的抗核小体抗体。将高滴度抗SS-A/Ro抗体阳性患者的单个核细胞转移到SCID小鼠体内，诱发皮肤病变。我们的数据显示，转基因小鼠在皮肤-表皮交界处出现轻微红斑和脱发，没有免疫球蛋白和/或补体成分沉积。信号转导系统目前正在研究中。

项目成果

Tokura Y,Furukawa F 他: "Lyirphocytes stimulation test with drug -photomodified cells in patients with quinolone photosensitivity"Journal of Dermatological Science. 21. 34-41 (1999)

Tokura Y、Furukawa F 等人：“喹诺酮光敏性患者的淋巴细胞刺激试验”，《皮肤病学杂志》21. 34-41 (1999)。

Furukawa F: "Antinulear antibody-keratinocyte interactions in photo sensitive lupus"Histology Histopathology. 14. 627-633 (1999)

Furukawa F：“光敏性狼疮中的抗核抗体-角质形成细胞相互作用”组织学组织病理学。

古川福実: "SLEと光線過敏"Junior. No.400. 9-13 (2001)

古川福美：“SLE 和光敏性”Junior 9-13 (2001)。

Furukawa F 他5名: "Keratinocytes from patients with lupus erythmatosus・・・・"Clin Exp Immunol. 118. 164-170 (1999)

Furukawa F 和其他 5 人：“红斑狼疮患者的角质形成细胞……”Clin Exp Immunol。118. 164-170 (1999)

Seo N, F Furukawa 他4名: "Percutaneous peptide immunization via corneum・・・"Proc Natl Acad Sci USA. 97. 371-376 (2000)

Seo N、F Furukawa 等 4 人：“通过角质进行经皮肽免疫……”Proc Natl Acad Sci USA 97. 371-376 (2000)。