THE PATHOGENIC EFFECT OF IGG4 AUTOANTIBODIES IN ENDEMIC PEMPHIGUS FOLIACEUS (FOGO SELVAGEM)
THE PATHOGENIC EFFECT OF IGG4 AUTOANTIBODIES IN ENDEMIC PEMPHIGUS FOLIACEUS (FOGO SELVAGEM)
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DOI：
10.1056/nejm198906013202206
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发表时间：
1989-06-01
影响因子：
158.5
通讯作者：
DIAZ, LA
中科院分区：
文献类型：
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作者：
ROCK, B;MARTINS, CR;DIAZ, LA
地方性落叶型天疱疮，或称fogo selvagem，是一种自身免疫性起泡性皮肤病，由桥粒相关糖蛋白的IgG自身抗体引起。我们研究了29例活动性疾病患者血清中的自身抗体活性的IgG亚类，并在18例患者的皮肤病变的免疫荧光，使用IgG亚类特异性单克隆抗体。所有患者中存在的主要疾病自身抗体均为IgG 4亚类。IgG 1和IgG 2自身抗体在29例患者中检测到低滴度：IgG 1 23例，IgG 2 9例。在任何患者的血清中均未检测到IgG 3自身抗体。皮肤病变的直接免疫荧光检测显示角质形成细胞表面上的IgG 4的优先沉积。IgG 4的致病作用通过将患者体内含有IgG 4自身抗体的组分被动转移至新生BALB/c小鼠来证明。在这些动物中，患者的疾病在临床上、组织学上和免疫学上再现。只有IgG 4自身抗体被检测到直接免疫荧光，结合到表皮病变的小鼠，并通过免疫电子显微镜在角质形成细胞表面。先前已报道IgG 4是阻断性或保护性抗体，因为与其它IgG亚类相比，其在体外具有较差的效应子功能。它是fogo selvagem中的致病性自身抗体的发现提高了它在其他自身免疫性疾病中也可能很重要的可能性。
Endemic pemphigus foliaceus, or fogo selvagem, is an autoimmune blistering skin disease caused by IgG autoantibodies to a desmosome-associated glycoprotein. We studied the IgG subclasses with autoantibody activity in serum from 29 patients with active disease and in the skin lesions of 18 patients by immunofluorescence, using IgG-subclass-specific monoclonal antibodies. The predominant disease autoantibodies present in all patients were of the IgG4 subclass. IgG1 and IgG2 autoantibodies were detected in low titer in the 29 patients: IgG1 in 23 patients and IgG2 in 9. IgG3 autoantibodies were not detected in the serum of any patient. Direct immunofluorescence testing of skin lesions showed a preferental deposition of IgG4 on the keratinocyte surface. The pathogenic effect of IgG4 was demonstrated by the passive transfer of fractions containing IgG4 autoantibodies from the patients to neonatal BALB/c mice. The disease of the patients was reproduced clinically, histologically, and immunologically in these animals. Only IgG4 autoantibodies were detected by direct immunofluorescence, bound to the epidermis in the lesions of the mice, and by immunoelectron microscopy at the keratinocyte surface. IgG4 has previously been reported to be a blocking or protective antibody because it has poor effector functions in vitro, as compared with the other IgG subclasses. The finding that it is the pathogenic autoantibody in fogo selvagem raises the possibility that it may also be important in other autoimmune disease.