Defining the pathogenic involvement of desmoglein 4 in pemphigus and staphylococcal scalded skin syndrome
Defining the pathogenic involvement of desmoglein 4 in pemphigus and staphylococcal scalded skin syndrome
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DOI：
10.1172/jci200420480
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发表时间：
2004-11-01
影响因子：
15.9
通讯作者：
Amagai, M
中科院分区：
文献类型：
--
作者：
Nagasaka, T;Nishifuji, K;Amagai, M
桥粒芯糖蛋白（Desmogleins，Dsgs）是一种钙粘蛋白型细胞粘附分子，是天疱疮和葡萄球菌等皮肤水疱性疾病的靶向分子。烫伤皮肤综合征（SSSS）。研究了Dsg 4（一种新的同种型）在这些疾病中的作用。Dsg 4被39份含有抗Dsg 1 IgG的天疱疮血清中的30份（77%）识别，但不被16份不含抗Dsg 1 IgG的天疱疮血清或34份正常对照血清识别。这些血清的Dsg 4免疫反应性通过去除抗Dsg 1 IgG而被消除。相反，从天疱疮血清中去除抗Dsg 4 IgG仅使针对Dsg 1的免疫反应性降低13.8% +/-8.8%（n = 23），并且不影响其在新生小鼠中诱导水疱的能力。在Dsg 4上亲和纯化的IgG识别Dsg 1，但不能诱导水疱，而在Dsg 1上从相同的落叶型天疱疮血清中纯化的IgG诱导水疱。因此，天疱疮血清由于抗Dsg 1 IgG亚群的交叉反应性而显示出Dsg 4反应性，并且Dsg 4/Dsg 1交叉反应IgG没有可证实的致病作用。此外，Dsg 4不被在SSSS中诱导水泡的脱落毒素切割。这些研究结果表明，Dsg 4可能发挥的作用以外的粘附和桥粒芯糖蛋白自身抗体的交叉反应性，应考虑到天疱疮的自身免疫机制的未来研究的框架。
Desmogleins (Dsgs), cadherin-type cell adhesion molecules, are targeted in skin-blistering diseases such as pemphigus and staphylococcal. scalded skin syndrome (SSSS). The role of Dsg4, a new isoform, was investigated in these diseases. Dsg4 was recognized by 30 (77%) of 39 pemphigus sera containing anti-Dsg1 IgG but not by 16 pemphigus sera containing no anti-Dsg1 IgG or by 34 normal control sera. The Dsg4 immunoreactivity of these sera was abolished by removal of anti-Dsg1 IgG. Conversely, the removal of anti-Dsg4 IgG from pemphigus sera reduced the immunoreactivity against Dsg1 only 13.8% +/- 8.8% (n = 23) and did not affect its ability to induce blisters in neonatal mice. IgG that was affinity-purified on Dsg4 recognized Dsg1 but failed to induce blisters, while IgG purified on Dsg1 from the same pemphigus foliaceus sera induced blisters. Thus, pemphigus sera show Dsg4 reactivity due to cross-reactivity of a subset of anti-Dsg1 IgG, and the Dsg4/Dsgl-cross-reacting IgG has no demonstrable pathogenic effect. In addition, Dsg4 was not cleaved by exfoliative toxins that induce blisters in SSSS. These findings suggest that Dsg4 may play a role other than adhesion and that the cross-reactivity of desmoglein autoantibodies should be factored into the framework of future studies of autoimmune mechanisms in pemphigus.