Experimental Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany.
Brain Behav Immun. 2012 Jan;26(1):96-102. doi: 10.1016/j.bbi.2011.07.241. Epub 2011 Aug 6.
Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Autoantibody based immune processes are assumed to be involved in its pathogenesis. However, it is still unclear to what extent autoantibody patterns found in the eye (aqueous humor) are congruent to systemic autoantibodies (blood). Consistency would underline the specificity of known serum antibody markers for glaucoma. In this study we used antigen microarrays to analyze autoantibody reactivities in sera and corresponding aqueous humor samples of primary open-angle glaucoma patients (N=37) and non-glaucomatous controls (N=31). Compared to control subjects several divergent immunoreactivities were identified for the glaucoma group in both body fluids. Interestingly, 20% of the tested antigens revealed increased immunoreactivities (e.g., against HSP27, MBP, and α-1-antitrypsin) and 7.5% decreased immunoreactivities (e.g., against GFAP and β-L-crystallin), thus demonstrating a significant alteration of the autoantibody profiles in glaucoma patients. Using an artificial neural network in combination with a unique serum autoantibody pattern on prospective sera we were able to detect glaucoma with a specificity and sensitivity of approximately 93%. The intraindividual comparison revealed a strong correlation of detected immunoreactivities in sera and comparative aqueous humor samples in both study groups. These results emphasize the specificity of immunoreactions found in blood samples of glaucoma patients. Furthermore they indicate the necessity of analyzing not only up-regulated but also down-regulated antibody reactivities, which might be likewise relevant for the understanding of other diseases.
青光眼是一种慢性神经退行性疾病，也是导致失明的主要原因之一。人们认为自身抗体免疫过程与它的发病机制有关。然而，眼部（房水）中发现的自身抗体模式与系统性自身抗体（血液）在多大程度上一致仍不清楚。一致性将强调已知血清抗体标志物对青光眼的特异性。在这项研究中，我们使用抗原微阵列分析了原发性开角型青光眼患者（N=37）和非青光眼对照者（N=31）的血清和相应房水样本中的自身抗体反应。与对照组相比，两组体液中均鉴定出几种不同的免疫反应性。有趣的是，20%的测试抗原显示出增加的免疫反应性（例如，针对 HSP27、MBP 和 α-1-抗胰蛋白酶）和 7.5%的免疫反应性降低（例如，针对 GFAP 和 β-L-晶体蛋白），从而表明青光眼患者的自身抗体谱发生了显著改变。使用人工神经网络结合独特的血清自身抗体模式对前瞻性血清进行分析，我们能够以约 93%的特异性和敏感性检测出青光眼。个体内比较显示，两组研究中血清和比较房水样本中检测到的免疫反应性具有很强的相关性。这些结果强调了在青光眼患者的血液样本中发现的免疫反应的特异性。此外，它们还表明不仅需要分析上调的抗体反应，还需要分析下调的抗体反应，这对于理解其他疾病也可能同样重要。
