Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.
Legacy Devers Eye Institute, Portland, OR, USA.
Eye (Lond). 2024 Feb;38(2):386-392. doi: 10.1038/s41433-023-02706-6. Epub 2023 Aug 19.
Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor.
SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory.
We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase.
A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.
自身免疫和转录因子自身免疫调节蛋白（AIRE）的缺乏与唐氏综合征（DS）有关。缺乏 AIRE 会破坏胸腺耐受。与 DS 相关的自身免疫性眼病尚未得到描述。我们鉴定了一系列患有 DS（n=8）和葡萄膜炎的患者。在连续的三个患者中，我们检验了自身免疫性视网膜抗原可能是一个致病因素的假设。
患者/方法：这是一项多中心、回顾性病例系列研究。通过葡萄膜炎专科医生的问卷调查收集了具有 DS 和葡萄膜炎的患者的匿名临床数据。使用在 OHSU 眼免疫实验室测试的自身免疫性视网膜抗体试剂盒检测抗视网膜抗体（AAb）。
我们描述了 8 例患者（平均年龄 29 岁[范围 19-37 岁]）。葡萄膜炎发病的平均年龄为 23.5 岁[范围 11-33 岁]。所有 8 例患者均患有双侧葡萄膜炎（与文献报道的大学转诊模式相比，p<0.001），6 例和 5 例患者分别出现前葡萄膜炎和中间葡萄膜炎。3 例接受抗视网膜 AAb 检测的患者均为阳性。检测到的 AAb 包括抗碳酸酐酶 II、烯醇化酶、 arrestin 和醛缩酶。
在 DS 中已描述了 21 号染色体上 AIRE 的部分缺失。在这个患者组中葡萄膜炎表现的相似性、DS 中的已知自身免疫疾病易感性、DS 和 AIRE 缺乏的已知关联、一般来说 DS 患者中报道的抗视网膜抗体的检测、以及我们研究中三个患者存在抗视网膜 AAb，均支持 DS 与自身免疫性眼病之间的因果关联。
