Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
J Clin Immunol. 2012 Dec;32(6):1213-20. doi: 10.1007/s10875-012-9744-6. Epub 2012 Jul 31.
To describe a case of autosomal-dominant (AD)-chronic mucocutaneous candidiasis (CMC) with a signal transducer and activator of transcription (STAT) 1 gene mutation, and some of the important complications of this disease such as chronic hepatitis.
We present a 23-year-old woman with CMC, chronic active hepatitis, and hypothyroidism. Her father also had CMC. We performed several immunological analyses of blood and liver samples, and searched for gene mutations for CMC in the patient and her father.
We identified the heterozygous substitution c.821 G > A (p.Arg274Gln) in the STAT1 gene of both the patient and her father. The level of β-glucan induced interferon (IFN)-γ in her blood cells was significantly low. Immunoblot analysis detected serum anti-interleukin (IL)-17 F autoantibody. She was found to have increased (low-titer) antibodies related to her hypothyroidism and hepatitis. Her serum IL-18 levels fluctuated with her AST and ALT levels. Liver biopsy revealed CD68-positive cell infiltration and IL-18 expression in the sinusoidal regions. These results suggest that the chronic active hepatitis in this patient may be exacerbated by the excessive IL-18 accumulation caused by recurrent mucocutaneous fungal infection, and decreased IFN-γ production.
AD-CMC is known to be caused by a gain-of-function mutation of the STAT1 gene. Chronic active hepatitis is a rare complication of AD-CMC, with currently unknown pathogenesis. It seems that the clinical phenotype in this patient is modified by autoimmune mechanisms and cytokine dysregulation. AD-CMC can be complicated by various immune disorders including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
描述一例常染色体显性（AD）-慢性黏膜皮肤念珠菌病（CMC）伴信号转导和转录激活因子（STAT）1 基因突变，并介绍该病的一些重要并发症，如慢性肝炎。
我们报告了一例 23 岁女性患者，患有 CMC、慢性活动性肝炎和甲状腺功能减退症。她的父亲也患有 CMC。我们对患者和她父亲的血液和肝脏样本进行了多项免疫分析，并寻找 CMC 的基因突变。
我们在患者和她父亲的 STAT1 基因中发现了杂合性取代 c.821G>A（p.Arg274Gln）。她的血细胞中β-葡聚糖诱导的干扰素（IFN）-γ水平显著降低。免疫印迹分析检测到血清抗白细胞介素（IL）-17F 自身抗体。发现她患有与甲状腺功能减退症和肝炎相关的增加（低滴度）抗体。她的血清 IL-18 水平随 AST 和 ALT 水平波动。肝活检显示 CD68 阳性细胞浸润和窦状区 IL-18 表达。这些结果表明，该患者的慢性活动性肝炎可能由于反复黏膜皮肤真菌感染引起的 IL-18 过度积累和 IFN-γ产生减少而加重。
AD-CMC 已知由 STAT1 基因的功能获得性突变引起。慢性活动性肝炎是 AD-CMC 的罕见并发症，目前发病机制尚不清楚。似乎该患者的临床表型受自身免疫机制和细胞因子失调的修饰。AD-CMC 可并发各种免疫紊乱，包括自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良。
