Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Adv Exp Med Biol. 2018;1074:193-201. doi: 10.1007/978-3-319-75402-4_24.
Autoimmune retinopathy (AIR) was often mistaken for retinitis pigmentosa (RP), due to an overlap of clinical findings, but increasingly has been recognized as a unique entity in the last decade. AIR has distinctive features: sudden onset of photopsias and scotomata in patients with no family history of RP, followed by visual field and central vision loss. Initially, retina exams are normal with no sign of pigment deposits or retinal degeneration. A family history of autoimmune diseases (all types) occurs in 60% of patients. One hallmark of AIR has been the presence of anti-retinal autoimmune antibodies (ARAs) in patients' sera, but patients can continue to have ARAs even when the disease has been quiescent for years. The accumulation of ARAs represents a breakdown of retinal immune tolerance with many different immunoreactive bands found at different reference weights in AIR patients. We began investigating cellular immunity using flow cytometry and found abnormal distributions (>2 StDev) of increased memory lymphocytes and NK cells and decreased regulatory B cell subsets in many AIR patients compared to normal controls. Culture of patient lymphocytes with small amounts (25 μg) of recoverin protein for 6 days led to significant elevations of interferon gamma (IFNγ) and in some cases tumor necrosis factor alpha (TNFα) production. We found the IFNγ/IL-10 ratio in response to recoverin was elevated in patients with more active disease (defined by visual field contraction between visits), but in some patients, there also appeared to be independent factors influencing severity, suggesting other autoimmune mechanisms were at play. These cellular immune parameters may provide improved markers for active AIR.
自身免疫性视网膜炎（AIR）常因临床表现重叠而被误诊为色素性视网膜炎（RP），但在过去十年中，它越来越被认为是一种独特的疾病。AIR 具有独特的特征：无 RP 家族史的患者突然出现光幻视和暗点，随后出现视野和中心视力丧失。最初，视网膜检查正常，无色素沉着或视网膜变性迹象。60%的患者有自身免疫性疾病（所有类型）家族史。AIR 的一个标志是患者血清中存在抗视网膜自身抗体（ARAs），但即使疾病多年处于静止状态，患者仍可能继续存在 ARAs。ARAs 的积累代表了视网膜免疫耐受的破坏，在 AIR 患者中发现了许多不同的免疫反应性带，具有不同的参考重量。我们开始使用流式细胞术研究细胞免疫，发现与正常对照组相比，许多 AIR 患者的记忆淋巴细胞和 NK 细胞分布异常（>2StDev），调节性 B 细胞亚群减少。与少量（25μg）回收蛋白孵育患者淋巴细胞 6 天后，干扰素 γ（IFNγ）显著升高，在某些情况下肿瘤坏死因子 α（TNFα）也显著升高。我们发现，对回收蛋白的 IFNγ/IL-10 比值在疾病更活跃的患者中升高（定义为随访期间视野收缩），但在一些患者中，似乎还有其他影响严重程度的独立因素，表明存在其他自身免疫机制。这些细胞免疫参数可能为活动性 AIR 提供更好的标志物。
