Yang Sufang, Dizhoor Alexander, Wilson David J, Adamus Grazyna
Casey Eye Institute, School of Medicine, Oregon Health and Science University, Portland, OR, USA.
Department of Research, Salus University, Elkins Park, PA, USA.
Transl Vis Sci Technol. 2016 May 2;5(3):1. doi: 10.1167/tvst.5.3.1. eCollection 2016 May.
Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients' AAbs.
Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A).
Among the cohort of 173 patients, only 68 had anti-recoverin AAbs and the remaining 105 reacted with 4 unique proteins, which were identified as a Rab6A, HSP27, GCAP1, and GCAP2. Confocal images from a double labeling study confirmed the reactivity of AAbs with different types of cells in human retina, consistent with the target protein's respective cellular functions. Patients (62/173) had been diagnosed with various kinds of cancer, including 20% of patients who had anti-recoverin, 11% anti-Rab6A, and 5% anti-HSP27 AAbs. Only 50% of recoverin-seropositive patients had cancer and the individuals with anti-recoverin AAbs had a significantly higher likelihood to be diagnosed with cancer than patients with other anti-23-kDa AAbs.
The newly discovered retinal autoantigens may be involved in pathogenicity of CAR and AR. The recognition of AAbs against various retinal proteins associated with autoimmune retinal degeneration broadens the group of proteins related with these entities.
Patients with anti-recoverin, anti-GCAP1, anti-Rab6A, and anti-HSP27 AAbs represented diverse clinical phenotypes, so the presence of disease-associated AAbs provides important information for molecular diagnosis.
癌症相关性视网膜病变（CAR）和自身免疫性视网膜病变（AR）中报道了具有不同视网膜特异性的自身抗体（AAb）。目标是鉴定患者AAb常识别的表观分子量为23 kDa的小视网膜蛋白。
通过蛋白质印迹法和双免疫荧光共聚焦显微镜对173例患者针对23 kDa视网膜蛋白的血清进行回顾性研究。蛋白质组学分析揭示了新的23 kDa蛋白候选物，包括鸟苷酸环化酶激活蛋白（GCAP）、热休克蛋白27（HSP27）和Rab6A GTP酶（Rab6A）。
在173例患者队列中，仅68例有抗恢复蛋白AAb，其余105例与4种独特蛋白发生反应，这些蛋白被鉴定为Rab6A、HSP27、GCAP1和GCAP2。双标记研究的共聚焦图像证实了AAb与人视网膜中不同类型细胞的反应性，这与靶蛋白各自的细胞功能一致。患者（62/173）已被诊断患有各种癌症，包括20%有抗恢复蛋白、11%有抗Rab6A和5%有抗HSP27 AAb的患者。只有50%的恢复蛋白血清阳性患者患有癌症，且抗恢复蛋白AAb的个体被诊断患有癌症的可能性显著高于其他抗23 kDa AAb的患者。
新发现的视网膜自身抗原可能参与CAR和AR的发病机制。针对与自身免疫性视网膜变性相关的各种视网膜蛋白的AAb的识别拓宽了与这些实体相关的蛋白组。
抗恢复蛋白、抗GCAP1、抗Rab6A和抗HSP27 AAb的患者表现出不同的临床表型，因此疾病相关AAb的存在为分子诊断提供了重要信息。
