Efficacy of intravenous immunoglobulin (IVIG) affinity-purified anti-desmoglein anti-idiotypic antibodies in the treatment of an experimental model of pemphigus vulgaris.
Efficacy of intravenous immunoglobulin (IVIG) affinity-purified anti-desmoglein anti-idiotypic antibodies in the treatment of an experimental model of pemphigus vulgaris.
复制标题
静脉注射免疫球蛋白（IVIG）亲和纯化的抗桥粒芯糖蛋白抗独特型抗体在治疗寻常型天疱疮实验模型中的功效。
DOI：
10.1111/j.1365-2249.2010.04265.x
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发表时间：
2010
影响因子：
4.6
通讯作者：
Shoenfeld,Y
中科院分区：
文献类型：
--
作者：
Mimouni,D;Blank,M;Payne,AS;Anhalt,GJ;Avivi,C;Barshack,I;David,M;Shoenfeld,Y
寻常天疱疮是一种罕见的危及生命的自身免疫性大疱性疾病，由针对桥粒核心糖蛋白1和3的免疫球蛋白G（IgG）自身抗体引起。以前，我们表明静脉注射免疫球蛋白（IVIG）改善抗桥粒芯蛋白诱导的实验性寻常天疱疮新生小鼠。本研究的目的是检查抗-抗-桥粒核心蛋白特异性IVIG在类似模型中的功效。寻常型天疱疮特异性IVIG（PV-sIVIG）在单链可变片段（scFv）抗桥粒核心糖蛋白1和3的柱上从IVIG亲和纯化。酶联免疫吸附试验、抑制试验证实PV-sIVIG具有抗独特型活性。在通过向新生小鼠注射抗桥粒核心糖蛋白1和3scFv诱导天疱疮后，用PV-sIVIG、IVIG（低或高剂量）或来自健康供体的IgG（每种n= 10）处理动物。24-48 h后取皮肤组织进行组织学和免疫荧光分析，结果表明，PV-sIVIG能明显抑制抗桥粒芯糖蛋白1和3单链抗体与重组桥粒芯糖蛋白3的结合，并呈剂量依赖性。在体内分析显示寻常型天疱疮皮肤病变的小鼠注射正常IgG（9/10的小鼠）或低剂量IVIG（9/10的小鼠），但不是在小鼠PV-sIVIG（10）或高剂量IVIG（10）治疗。免疫病理学研究表明，PV-sIVIG和常规IVIG可防止棘层松解症的形成和IgG在细胞间隙的沉积。总之，PV-sIVIG制剂在抑制抗桥粒芯蛋白诱导的小鼠寻常型天疱疮方面比天然IVIG更有效，并且可能作为临床疾病患者的未来治疗。
Pemphigus vulgaris is a rare life-threatening autoimmune bullous disease caused by immunoglobulin G (IgG) autoantibodies directed against desmogleins 1 and 3. Previously, we showed that intravenous immunoglobulin (IVIG) ameliorates anti-desmoglein-induced experimental pemphigus vulgaris in newborn naive mice. The aim of this study was to examine the efficacy of anti-anti-desmoglein-specific IVIG in a similar model. Pemphigus-vulgaris-specific IVIG (PV-sIVIG) was affinity-purified from IVIG on a column of single-chain variable fragment (scFv) anti-desmogleins 1 and 3. The anti-idiotypic activity of PV-sIVIG was confirmed by enzyme-linked immunosorbent assay, inhibition assay. After induction of pemphigus by injection of anti-desmogleins 1 and 3 scFv to newborn mice, the animals were treated with PV-sIVIG, IVIG (low or high dose) or IgG from a healthy donor (n= 10 each). The skin was examined 24–48 h later, and samples of affected areas were analysed by histology and immunofluorescence.In vitrostudy showed that PV-sIVIG significantly inhibited anti-desmogleins 1 and 3 scFv binding to recombinant desmoglein-3 in a dose-dependent manner. Specificity was confirmed by inhibition assay.In vivoanalysis revealed cutaneous lesions of pemphigus vulgaris in mice injected with normal IgG (nine of 10 mice) or low-dose IVIG (nine of 10 mice), but not in mice treated with PV-sIVIG (none of 10) or high-dose IVIG (none of 10). On immunopathological study, PV-sIVIG and regular IVIG prevented the formation of acantholysis and deposition of IgG in intercellular spaces. In conclusion, the PV-sIVIG preparation is more effective than native IVIG in inhibiting anti-desmoglein-induced pemphigus vulgaris in mice and might serve as a future therapy in patients with the clinical disease.