Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy.
Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy.
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DOI：
10.1186/1471-2415-4-5
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发表时间：
2004-06-04
影响因子：
2
通讯作者：
Weleber, Richard G
中科院分区：
文献类型：
--
作者：
Adamus, Grazyna;Ren, Gaoying;Weleber, Richard G
背景技术背景：自身免疫性视网膜变性可能发生在通过抗视网膜蛋白的自身抗体的作用而呈现与异常ERG相关的视网膜起源的突然或较不常见的亚急性视力丧失的患者中。通常，患者最初被诊断为或怀疑患有副肿瘤性视网膜病变（PR），如癌症相关视网膜病变（CAR）。然而，关于这些患者自身抗体的发生、特异性及其与临床症状的关系的信息有限。从193名视网膜病患者获得血清，这些患者表现出类似PR或自身免疫性视网膜病（AR）的临床症状，包括通常与视野缺陷和视网膜病变相关的突然无痛性视力丧失，以及视网膜电图（ERG）上的异常视杆和/或视锥反应。通过使用从人视网膜提取的蛋白质的Western印迹分析和通过免疫组织化学来测试血清中抗视网膜自身抗体的存在。用ELISA法测定针对recoverin和enolase.RESULTS的自身抗体滴度：我们发现视网膜病变患者中抗视网膜自身抗体的患病率较高。91例患者（47.1%）的血清显示各种特异性的自身抗体，诊断为癌症的视网膜病变患者（33/52; 63.5%; p = 0.009）中存在的抗体发生率高于非癌症视网膜病变患者（58/141; 41.1%）。PR患者的平均年龄为62.0岁，AR患者的平均年龄为55.9岁。针对恢复素（p23）的自身抗体仅存在于PR患者的血清中，针对未知p35的自身抗体在AR患者中更常见，而抗烯醇化酶（抗p46）自身抗体在PR患者和AR患者的血清中几乎相等地分布。在血清反应阳性的患者中，自身抗体持续了很长一段时间--从数月到数年。发现抗恢复素自身抗体滴度的反弹与视觉症状的加重有关，但与癌症复发无关。当从健康受试者的血清相比，从两组患者的视网膜蛋白的自身抗体是细胞毒性的视网膜细胞，表明其致病potential.CONCLUSIONS：这些研究表明，患者突然或亚急性，原因不明的视力丧失的视网膜起源有抗视网膜抗体在广泛的特异性，并表明需要进行自身抗体筛查。抗体水平的后续测试可能是有用的，作为与视力恶化相关的疾病活动的生物标志物。此外，自身抗体特异性的异质性可以解释视网膜病变患者临床症状的多样性和复杂性。
BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms.METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA.RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time--from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential.CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients.