寻常型天疱疮抗原细胞外区1～2表位抗体亚型的致病性

Pathogenicity of Antibody Subtypes against Pemphigus Vulgaris Antigen Extracellular 1-2 Epitopes

目的探讨不同寻常性天疱疮(PV)抗体亚型在PV中的作用。方法分别用完全弗氏佐剂(CFA)、铝[Al(OH)3]佐剂联合重组寻常型天疱疮抗原(PVA)细胞外区1～2融和蛋白免疫C57BL/6小鼠。免疫后对其细胞因子的类别、特异性抗体滴度和抗体亚型进行检测;并通过诱导新生鼠的动物模型评价其致病性。结果免疫后经细胞因子检测显示CFA组小鼠产生较多的Th1型细胞因子γ-干扰素(IFNγ),Al(OH)3组则以Th2型细胞因子白介素-4(IL-4)为主;抗体亚型的型别在CFA组中以IgG2a为主,而Al(OH)3组以IgG1为主。新生鼠被动转移实验显示,转移Al(OH)3组小鼠的抗血清可使被转移鼠皮肤出现糜烂,组织病理、免疫荧光均符合PV的表现,而CFA组小鼠的抗血清不能出现上述表现。结论相同PVA在不同免疫佐剂作用下可诱导产生不同抗体亚型;不同亚型的抗PVA抗体其致病性不同。

Objective To explore whether the antibody subtypes against the extracellular 1-2 （EC1-2） epitopes of pemphigus vulgaris antigen （PVA） are related to the pathogenesis of PVA. Methods EC1-2 fusion protein, emulsified with complete Freund＇s adjuvant （CFA） or aluminum hydroxide hydrate [ Al（ OH）3 ], was used to immunize C57BL/6 mouse. After immunization, the cytokine types, specific antibody titers, and antibody subtypes were detected. Also, a neonatal mice model was used to evaluate the pathogenesis of different antibodies. Results Thl type cytokine interferon γ （IFNγ） was elevated in CFA group, while Th 2 type cytokine interleukin-4 （IL-4） was increased in Al （OH）3 group. The antibody subtypes were different in both groups. After the two groups were transferred with antisera separately, the neonatal mice developed erosion on the skin from AI（OH）3 group, with acantholysis histopathologically and bright immuno-fluorescence deposition, which was not seen in CFA group. Conclusion Different antibody subtypes may contribute to the pathogenesis of disease.