Inborn errors of immunity offer important insights to mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1) chronic mucocutaneous candidiasis has been ascribed to neutralizing IL-17 autoantibodies. Recent evidence implicates ecxessive T-cell IFN-γ secretion ensuing epithelial barrier disruption in predisposition to candidiasis, but these results remain to be replicated. It is debated whether IL-17 paucity, increased type I inflammation or their combination underlies susceptibility to chronic mucocutaneus candidiasis in APS-1. To characterize the immunological features in cervicovaginal mucosa of females with APS-1. Vaginal fluid was collected with flocked swab from 17 females with APS-1 and 18 controls and cytokine composition analysed using Luminex. Cervical cell sample was obtained with a cervix brush from six patients and six healthy controls and subjected to transcriptome analysis. The vaginal fluid from patients with APS-1 had IFN-γ concentration comparable to controls (2.6 vs 2.4 pg/ml), but contained high concentrations of Th1 chemokines CXCL9 and CXCL10 (1094 vs 110 pg/ml; p<0.001 and 4033 vs 273 pg/ml; p=0.001, respectively) while IL-17 levels were comparable (28 vs 8.8 pg/ml). RNAseq of cervical cells revealed upregulation of pathways related to mucosal inflammation and cell death in the patients. Excessive Th1 response appears to underlie disruption of the mucosal immune responses in genital tract of patients with APS-1 and may contribute to susceptibility to candidiasis also in genital tract.

中文翻译：

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APS-1 患者妇科宫颈阴道样本中 1 型炎症增加

先天性免疫错误为粘膜免疫提供了重要的见解。在 1 型自身免疫性多内分泌综合征 (APS-1) 中，慢性皮肤粘膜念珠菌病被归因于中和 IL-17 自身抗体。最近的证据表明，T 细胞 IFN-γ 分泌过多，导致上皮屏障破坏，易患念珠菌病，但这些结果仍有待重复。IL-17 缺乏、I 型炎症增加或它们的组合是否是 APS-1 中慢性皮肤粘膜念珠菌病易感性的基础，这一点存在争议。表征 APS-1 女性宫颈阴道粘膜的免疫学特征。使用植绒拭子收集 17 名 APS-1 女性和 18 名对照女性的阴道液，并使用 Luminex 分析细胞因子组成。使用宫颈刷从六名患者和六名健康对照中获取宫颈细胞样本，并进行转录组分析。APS-1 患者的阴道液中 IFN-γ 浓度与对照组相当（2.6 vs 2.4 pg/ml），但含有高浓度的 Th1 趋化因子 CXCL9 和 CXCL10（1094 vs 110 pg/ml；p<0.001 和 4033 vs 273 pg/ml；p=0.001，分别），而 IL-17 水平相当（28 与 8.8 pg/ml）。宫颈细胞的 RNAseq 显示患者粘膜炎症和细胞死亡相关通路的上调。过度的 Th1 反应似乎是 APS-1 患者生殖道粘膜免疫反应破坏的基础，并且可能导致生殖道对念珠菌病的易感性。