Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions
Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions
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DOI：
10.1172/jci10305
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发表时间：
2000-12-01
影响因子：
15.9
通讯作者：
Grando, SA
中科院分区：
文献类型：
--
作者：
Nguyen, VT;Ndoye, A;Grando, SA
天疱疮是一种皮肤粘连的自身免疫性疾病，与针对许多角质形成细胞抗原的自身抗体相关，如粘附分子桥粒芯糖蛋白（Dsg）1。3和乙酰胆碱受体。认为抗Dsg抗体单独导致寻常型银屑病（PV）患者水疱的观点源于rDsg 1和rDsg 3吸收导致新生小鼠PV样皮肤水疱的抗体的能力。在这里，我们证明，从rDsg 1-Ig-His和rDsg 3-Ig-His凹槽的PV IgG显示相似的抗原谱，包括38-，43-，115-和190-kDa的角质形成细胞蛋白和非Dsg 3 130-kDa的多肽存在于角质形成细胞从Dsg 3敲除小鼠。我们将不与160-kDa Dsg 1或其45-kDa免疫反应性片段发生交叉反应且与重组Dsg I无反应性的PV IgG注射到Dsg 3缺失小鼠中。我们使用了具有Dsg 3基因的靶向突变的Dsg 3（无效）小鼠和在Dsg 3中携带自发无效突变的“秃顶”Dsg 3（bal）/Dsg 3（bal）小鼠。这些PV IgG引起皮肤大疱伴PV样基底上棘层松解和以渔网样图案染色的病灶周围表皮，表明PV表型可以在没有抗Dsg 3抗体的情况下诱导。也不需要抗Dsg 1抗体，因为其在PV IgG中的存在不会改变皮肤器官培养物中的PV样表型，并且因为箔状天疱疮IgG在Dsg 3（null）小鼠中产生不同的表型。因此，PV患者的皮肤粘膜病变可能由非Dsg抗体引起。
Pemphigus is an autoimmune disease of skin adhesion associated with autoantibodies against a number of keratinocyte antigens, such as the adhesion molecules desmoglein (Dsg) 1. and 3 and acetylcholine receptors. The notion that anti-Dsg antibodies alone are responsible for blisters in patients with permphigus vulgaris (PV) stems from the ability of rDsg1 and rDsg3 to absorb antibodies that cause PV-like skin blisters in neonatal mice. Here, we demonstrate that PV IgGs fluted from rDsg1-Ig-His and rDsg3-Ig-His show similar antigenic profiles, including the 38-, 43-, 115-, and 190-kDa keratinocyte proteins and a non-Dsg 3 130-kDa polypeptide present in keratinocytes from Dsg 3 knockout mouse. We injected into Dsg 3-lacking mice the PV IgGs that did not cross-react with the 160-kDa Dsg 1 or its 45-kDa immunoreactive fragment and that showed no reactivity with recombinant Dsg I. We used bo th the Dsg3(null) mice with a targeted mutation of the Dsg3 gene and the "balding" Dsg3(bal)/Dsg3(bal) mice that carry a spontaneous null mutation in Dsg3. These PV IgGs caused gross skin blisters with PV-like suprabasal acantholysis and stained perilesional epidermis in a Fishnet-like pattern, indicating that the PV phenotype can be induced without anti-Dsg 3 antibody. The anti-Dsg 1 antibody also was not required, as its presence in PV IgG does not alter the PV-like phenotype in skin organ cultures and because pemphigus foil aceus IgGs produce a distinct phenotype in Dsg3(null) mice. Therefore, mucocutaneous lesions in PV patients could be caused by non-Dsg antibodies.