TY - JOUR
T1 - Diversity in autoimmunity against retinal, neuronal, and axonal antigens in acquired neuro-retinopathy
AU - Adamus, Grazyna
AU - Brown, Lori
AU - Schiffman, Jade
AU - Iannaccone, Alessandro
N1 - Funding Information:
Acknowledgments The authors thank Dr. Larry David of the OHSU Proteomic Core Facility for his assistance in the MS/MS analysis of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) antigen. Special thanks to Dr. Sakir Humayun Gultekin, an OHSU Neuropathologist for his help in procuring a donor optic nerve tissue for the study. This work was supported by National Eye Institute Grants RO1 EY13053 (GA), R21 EY18416 (AI) and unrestricted RPB grants to CEI and HEI.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Autoantibodies
KW - Autoimmunity
KW - Immunofluorescence
KW - Neuropathy
KW - Optic nerve
KW - Retina
KW - Retinal degeneration
KW - Retinopathy
KW - Western blotting
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U2 - 10.1007/s12348-011-0028-8
DO - 10.1007/s12348-011-0028-8
M3 - Article
C2 - 21744285
AN - SCOPUS:84861190844
SN - 1869-5760
VL - 1
SP - 111
EP - 121
JO - Journal of Ophthalmic Inflammation and Infection
JF - Journal of Ophthalmic Inflammation and Infection
IS - 3
ER -