Diversity in autoimmunity against retinal, neuronal, and axonal antigens in acquired neuro-retinopathy

被引:35
作者
Adamus G. [1 ,4 ]
Brown L. [1 ]
Schiffman J. [2 ]
Iannaccone A. [3 ]
机构
[1] Casey Eye Institute, Oregon Health and Science University, Portland, OR
[2] Neuro-Ophthalmology, University of Texas M. D. Anderson Cancer Center, Houston, TX
[3] Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN
[4] Casey Eye Institute, BRB L467AD, Oregon Health and Science University, Portland, OR 97239
关键词
Autoantibodies; Autoimmunity; Immunofluorescence; Neuropathy; Optic nerve; Retina; Retinal degeneration; Retinopathy; Western blotting;
D O I
10.1007/s12348-011-0028-8
中图分类号
学科分类号
摘要
Purpose: Autoimmune retinopathies and optic neuropathies are complex disorders of the retina and the optic nerve, in which patients develop autoantibodies (AAbs) against retinal and optic nerve proteins. Autoimmunity might significantly influence the outcome of retinal and optic nerve degenerative process but the pathogenic process is not fully elucidated. To better understand the role of AAbs in pathogenicity of these suspected autoimmune visual disorders, we focused on unique AAbs specificities associated with the syndrome to identify their antigenic targets in the optic nerve and retina. Methods: Serum samples were obtained from patients, whose visual disorders were potentially autoimmune in nature, including patients with cancer with possible paraneoplastic syndrome. Autoantibodies were tested against human optic nerve and retinal antigens for specificity by Western blotting and immunofluorescence. Results: Out of 209 tested for anti-optic nerve autoantibodies, 55% showed specific neuronal autoantibodies. The repertoire of anti-optic nerve autoantibodies often differed from anti-retinal antibodies. The major antigenic targets for these antibodies could be divided into four groups. Autoantibodies specific to classical glycolytic enzymes involved in energy production (α and γ enolases, glyceraldehyde 3-phosphate dehydrogenase) also reacted with retinal antigens. Autoantibodies targeted neuronal-specific myelin proteins (MBP, MOG), aquaporin 4, and collapsing response mediator protein 5 reacted with optic nerve antigens. They showed immunostaining of axons and myelin in the optic nerve as determined by double immunofluorescence. Conclusion: We identified novel neuronal autoantigens not previously known to be associated with acquired autoimmune retinopathy and optic neuropathy. Knowledge of the full autoantibody repertoire perpetuating this syndrome is an important first requirement in increasing our understanding of the autoimmune process to facilitate better diagnosis, prognosis, and treatment. © 2011 The Author(s).
引用
收藏
页码:111 / 121
页数:10
相关论文
共 35 条
[1]  
Adamus G., Brown L., Weleber R.G., Molecular biomarkers for autoimmune retinopathies: significance of anti-transducin-alpha autoantibodies, Exp Mol Pathol, 87, 3, pp. 195-203, (2009)
[2]  
Adamus G., Ren G., Weleber R.G., Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy, BMC Ophthalmol, 4, 1, (2004)
[3]  
Chan J.W., Paraneoplastic retinopathies and optic neuropathies, Sur Ophthalmol, 48, 1, pp. 12-38, (2003)
[4]  
Frohman L., Dellatorre K., Turbin R., Bielory L., Clinical characteristics, diagnostic criteria and therapeutic outcomes in autoimmune optic neuropathy, Br J Ophthalmol, 93, 12, pp. 1660-1666, (2009)
[5]  
Damek D.M., Paraneoplastic retinopathy/optic neuropathy, Curr Treat Options Neurol, 7, 1, pp. 57-67, (2005)
[6]  
Goodwin J., Autoimmune optic neuropathy, Curr Neurol Neurosci Rep, 6, 5, pp. 396-402, (2006)
[7]  
Radhakrishnan S.S., Forma G., Carboni G., Mutolo M.G., Adamus G., Iannaccone A., Patterns of visual function loss in autoimmune neuro-retinopathy (AINR): psychophysical and electrophysiological findings, Invest Ophthalmol Vis Sci, 51, 5, (2010)
[8]  
Radhakrishnan S.S., Laing A.E., Adamus G., Iannaccone A., Clinical characteristics of patients with auto-immune retinopathies (AIR) and neuropathies (AIN): differential diagnosis with retinitis pigmentosa (RP), Invest Ophthalmol Vis Sci, 50, 5, (2009)
[9]  
Wax M.B., Yang J., Tezel G., Autoantibodies in glaucoma, Cur Eye Res, 25, 2, pp. 113-116, (2002)
[10]  
Joachim S.C., Pfeiffer N., Grus F.H., Autoantibodies in patients with glaucoma: a comparison of IgG serum antibodies against retinal, optic nerve, and optic nerve head antigens, Graefe's Arch Clin Exp Ophthalmol, 243, 8, pp. 817-823, (2005)