Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I
Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I
复制标题
DOI：
10.1084/jem.20091983
复制
发表时间：
2010-02-15
影响因子：
15.3
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
--
作者：
Puel, Anne;Doeffinger, Rainer;Casanova, Jean-Laurent
大多数患有I型自身免疫性多内分泌综合征（APS-I）的患者表现为慢性粘膜皮肤念珠菌病（CMC）。我们假设这种CMC可能是由于对白细胞介素（IL）-17细胞因子的自身免疫引起的。我们在所有33例受试患者的血清中发现了高滴度的抗IL-17 A、IL-17 F和/或IL-22的自身抗体（自身抗体），如通过基于多重粒子的流式细胞术检测到的。如Western印迹所示，针对IL-17 A、IL-17 F和IL-22的自身抗体在所测试的5名患者中是特异性的。如IL-17 A活性的生物测定所示，抗IL-17 A的自身抗体在唯一测试的患者中是中和的。37名健康对照者和103名患有其他自身免疫性疾病的患者中没有一人有这种自身抗体。APS-I患者中没有一个具有抗细胞因子的自身抗体，这些细胞因子先前被证明在其他患者中引起其他明确的临床综合征（IL-6、干扰素[IFN]-γ或粒细胞/巨噬细胞集落刺激因子）或针对其他细胞因子（IL-1 β、IL-10、IL-12、IL-18、IL-21、IL-23、IL-26、IFN-β、肿瘤坏死因子[α]或转化生长因子β）。这些发现表明，抗IL-17 A、IL-17 F和IL-22的自身抗体可能导致APS-I患者的CMC。
Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1 beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.