Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines.
Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines.
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DOI：
10.1084/jem.20091669
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发表时间：
2010-02-15
期刊：
影响因子：
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通讯作者：
Meager A
中科院分区：
文献类型：
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作者：
Kisand K;Bøe Wolff AS;Podkrajsek KT;Tserel L;Link M;Kisand KV;Ersvaer E;Perheentupa J;Erichsen MM;Bratanic N;Meloni A;Cetani F;Perniola R;Ergun-Longmire B;Maclaren N;Krohn KJ;Pura M;Schalke B;Ströbel P;Leite MI;Battelino T;Husebye ES;Peterson P;Willcox N;Meager A
慢性粘膜皮肤念珠菌病（CMC）经常与T细胞免疫缺陷有关。具体而言，促炎性IL-17 A产生的Th 17亚群涉及在上皮表面处针对真菌的保护。在自身免疫性多内分泌病念珠菌病外胚层营养不良（APECED，或自身免疫性多内分泌综合征1），CMC往往是第一个迹象，但潜在的免疫缺陷是一个长期存在的难题。相反，随后的内分泌功能明显是自身免疫性的，由自身免疫调节因子（AIRE）突变引起的胸腺自身耐受诱导缺陷引起。我们报告严重减少白念珠菌抗原和多克隆刺激与CMC的APECED患者的IL-17 F和IL-22的反应。令人惊讶的是，这些减少与IL-17 F和IL-22的中和自身抗体密切相关，而在没有CMC的APECED患者中，反应是正常的，并且自身抗体不常见。我们的多中心调查显示，在>150例APECED患者中，尤其是CMC患者中，存在针对IL-17 A（41%）、IL-17 F（75%）和/或IL-22（91%）的中和性自身抗体。我们独立地发现了对这些Th 17产生的细胞因子的自身抗体在罕见的胸腺瘤患者CMC。在所有提供信息的病例中，自身抗体先于CMC。我们的结论是，IL-22和IL-17 F是关键的天然防御CMC和免疫缺陷的基础CMC在两个患者组有自身免疫的基础。
Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.