寻常型天疱疮和叶状天疱疮患者抗桥霉素-3抗体的患病率和致病活性。

IF 11 1区 医学 Q1 DERMATOLOGY
Maud Maho-Vaillant, Alexandre Lemieux, Christophe Arnoult, Léopoldine Lebourgeois, Vivien Hébert, Thara Jaworski, Billal Tedbirt, Fabienne Jouen, Olivier Boyer, Sébastien Calbo, Pascal Joly, Marie-Laure Golinski
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引用次数: 0

摘要

背景:桥粒蛋白-3 (desmocolin -3, DSC3)是一种钙依赖性桥粒体钙粘蛋白,在细胞-细胞粘附中起重要作用。针对DSC3细胞外(EC)结构域的IgG抗体(Abs)偶尔在罕见类型的天疱疮中被检测到。对寻常型天疱疮和叶状天疱疮血清中抗ec -DSC3 IgG抗体和靶向DSC3细胞内(IC)结构域抗体的患病率及其潜在致病活性的研究,得出了相互矛盾的结果。目的:评估天疱疮患者针对DSC3的EC和IC结构域的抗体的患病率和致病性。方法:应用新开发的可寻址激光头免疫分析法检测146例天疱疮患者DSC3抗原EC和IC结构域的抗DSC3 IgG和IgA。这些自身抗体的致病性首先在体外通过角化细胞分离试验与患者血清或重组IC-DSC3免疫的C57BL/6小鼠的血清进行检测。通过将从杂交瘤(A9)中提取的抗ic - dsc3单克隆抗体(mAb)被动转移到新生小鼠体内,检测其体内致病性。结果:天疱疮患者血清中检测到抗ec - dsc3或抗ic - dsc3 IgG和/或IgA抗体的比例为21.2%,而健康供者血清中检测到抗ec - dsc3 IgG和/或IgA抗体的比例分别为4.0% (P < 0.001)和5.0% (P < 0.001)。大多数抗dsc3抗体对应IgA。根据代偿理论,在44%的天疱疮患者中检测到抗ic - dsc3抗体,其血清抗desmoglin (DSG) 1-3 Ab谱与其临床和组织学特征不一致。抗IC-DSC3 IgG和IgA抗体在体外诱导角质细胞单层解离,通过重组IC-DSC3预吸附这些IgG或IgA部分来消除。此外,重组IC-DSC3免疫小鼠的IgG体外诱导棘层溶解。最后,在新生小鼠中,抗ic - dsc3单抗与抗dsg1 -3抗体的被动转移加剧了水疱的形成。结论:我们的研究结果表明,抗ic - dsc3抗体具有致病性,并解释了一些患者在临床表型和抗dsg1 -3抗体谱方面的不一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prevalence and pathogenic activity of anti-desmocollin-3 antibodies in patients with pemphigus vulgaris and pemphigus foliaceus.

Background: Desmocollin-3 (DSC3) is a calcium-dependent desmosomal cadherin that plays an essential role in cell-cell adhesion. IgG antibodies (Abs) directed against the extracellular (EC) domain of DSC3 have occasionally been detected in rare types of pemphigus. Investigations into the prevalence of anti-EC-DSC3 IgG Abs and those targeting the intracellular (IC) domain of DSC3 in pemphigus vulgaris and pemphigus foliaceus sera, and their potential pathogenic activity, have yielded conflicting results.

Objectives: To assess the prevalence and pathogenicity of Abs directed against the EC and IC domains of DSC3 in patients with pemphigus.

Methods: Anti-DSC3 IgG and IgA directed against the EC and IC domains of DSC3 were assayed in 146 patients with pemphigus using a newly developed addressable laser bead immunoassay. The pathogenicity of these autoAbs was first tested in vitro using a keratinocyte dissociation assay with patients' sera or from C57BL/6 mice immunized with recombinant IC-DSC3. In vivo pathogenicity was tested by passive transfer of an anti-IC-DSC3 monoclonal Ab (mAb) derived from a hybridoma (A9) into neonatal mice.

Results: Anti-EC-DSC3 or anti-IC-DSC3 IgG and/or IgA Abs were detected in 21.2% of sera from patients with pemphigus vs. 4.0% (P < 0.001) and 5.0% (P < 0.001) of sera from healthy donors, respectively. Most anti-DSC3 Abs corresponded to IgA. Anti-IC-DSC3 Abs were detected in 44% of patients with pemphigus whose serum anti-desmoglein (DSG) 1-3 Ab profile was inconsistent with their clinical and histological features, according to compensation theory. Anti-IC-DSC3 IgG and IgA Abs induced a dissociation of the keratinocyte monolayer in vitro, which was abolished by preadsorption of these IgG or IgA fractions with recombinant IC-DSC3. In addition, IgG from mice immunized with recombinant IC-DSC3 induced acantholysis in vitro. Finally, in neonatal mice, the passive transfer of an anti-IC-DSC3 mAb in combination with anti-DSG1-3 Abs exacerbated blister formation.

Conclusions: Our findings suggest that anti-IC-DSC3 Abs are pathogenic and explain the discordance seen in some patients with regard to their clinical phenotype and their anti-DSG1-3 Ab profile.

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来源期刊
British Journal of Dermatology
British Journal of Dermatology 医学-皮肤病学
CiteScore
16.30
自引率
3.90%
发文量
1062
审稿时长
2-4 weeks
期刊介绍: The British Journal of Dermatology (BJD) is committed to publishing the highest quality dermatological research. Through its publications, the journal seeks to advance the understanding, management, and treatment of skin diseases, ultimately aiming to improve patient outcomes.
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