Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

Adamus, Grażyna

doi:10.3389/fimmu.2017.00505

Cited by 25 publications

(26 citation statements)

References 126 publications

(192 reference statements)

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“…Our patient’s examination findings of attenuated vessels with patchy RPE changes, as well as extensive loss of RPE cells and photorecep tors on histopathology, are typical of cancer-associated retinopathy/lymphoma-associated retinopathy [30-32]. GAPDH plays a central role in photoreceptor cell glycolysis and is the second most common antigenic target in autoimmune retinal diseases [33, 34]. Although cancer-associated retinopathy has been widely documented in patients with solid tumors of the breast, lung, and gynecologic system [35], reports of hematologic malignancies are quite rare [36, 37].…”

Section: Discussionmentioning

confidence: 99%

Beneath the Retinal Pigment Epithelium: Histopathologic Findings in Metastatic Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

McCall

Proia

2018

Ocul Oncol Pathol

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Purpose: To report a case of extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type metastatic to the space beneath the retinal pigment epithelium (RPE) with coincident paraneoplastic lymphoma-associated retinopathy. Methods: Findings of clinical and histopathologic examination are presented with differential diagnoses and a literature review. Case Report: A 53-year-old man presented with bilateral blindness and had exudative retinal detachments overlying subretinal masses in both eyes. Flow cytometry of pericardial fluid revealed malignant T lymphocytes. After two cycles of chemotherapy, the patient was hospitalized and quickly expired. Autopsy revealed lymphoma involving the eyes, heart, right lung, and two subcarinal lymph nodes focally. Histopathologic examination of the eyes revealed intraocular metastases from ENKTCL, nasal type. Expression of CD3 and CD56, along with expression of Epstein-Barr virus by in situ hybridization, confirmed the diagnosis. Lymphomatous infiltrates were confined to the space beneath the neurosensory retina and between the RPE and the Bruch membrane, sparing the uveal tissue, similar to other metastatic T-cell lymphomas. Extensive RPE and photoreceptor loss in regions with and without underlying tumor was typical of a concurrent paraneoplastic lymphoma-associated retinopathy. Conclusion: Patients diagnosed with ENKTCL should be evaluated by an ophthalmologist, as ophthalmic involvement portends a poor prognosis.

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Section: Discussionmentioning

confidence: 99%

Beneath the Retinal Pigment Epithelium: Histopathologic Findings in Metastatic Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

McCall

Proia

2018

Ocul Oncol Pathol

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“…An example of such cross-reactive antibodies is AAb against glycolytic enzymes, which have important metabolic functions in both microbial and retinal cells. Moreover, glycolytic proteins are multifunctional, they not only exist in the cytosol, but are also exposed on the membrane of microbes, making them easily accessible to the immune system ( 36 ).…”

Section: Generation Of Anti-retinal Aabsmentioning

confidence: 99%

“…However, sera of patients with CAR possess AAbs that not only react with photoreceptor cell antigens but also with bipolar and ganglion cells of the retina ( 62 , 66 , 73 , 74 ). AAbs against glycolytic enzymes, such as enolase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase M2, dominate in sera of patients with AR ( 36 ). Antibodies against heat shock proteins, such as heat shock protein 27 (HSP27) and HSP65, have also been detected in patients with CAR and AR ( 66 , 75 , 76 ).…”

Section: Retinal Autoantigensmentioning

confidence: 99%

“…Enolase-α is a major antigen in CAR and AR. Soon after its discovery, there was a concern about a broad association of anti-enolase-α AAbs in an autoimmunity that is not restricted to any particular disease, and is occasionally found in sera of normal individuals ( 36 , 112 ). Epitope mapping of CAR and normal sera revealed three binding regions of enolase within the amino acid residues 31–38 (FRAAVPSG), 176–183 (ANFREAMR), and 421–428 (AKFAGRNF), and these epitopes were common for all AAbs tested, independent of disease status ( 113 ).…”

Section: Importance Of Epitope Mapping In Armentioning

confidence: 99%

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Are Anti-Retinal Autoantibodies a Cause or a Consequence of Retinal Degeneration in Autoimmune Retinopathies?

Adamus

2018

Front. Immunol.

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Autoantibodies (AAbs) against various retinal proteins have been associated with vision loss in paraneoplastic and non-paraneoplastic autoimmune retinopathies (AR). There are two major paraneoplastic syndromes associated anti-retinal AAbs, cancer-associated retinopathy (CAR), and melanoma-associated retinopathy. Some people without a cancer diagnosis may present symptoms of CAR and have anti-retinal AAbs. The etiology and pathogenesis of those entities are not fully understood. In this review, we provide evidence for the role of AAbs in retinal death and degeneration. Studies of epitope mapping for anti-recoverin, anti-enolase, and anti-carbonic anhydrase II revealed that although patients’ AAbs may recognize the same retinal protein as normal individuals they bind to different molecular domains, which allows distinguishing between normal and diseased AAbs. Given the great diversity of anti-retinal AAbs, it is likely some antibodies have greater pathogenic potential than others. Pathogenic, but not normal antibodies penetrate the target cell, reach their specific antigen, induce apoptosis, and impact retinal pathophysiology. Photoreceptors, dying by apoptosis, induced by other than immunologic mechanisms produce substantial amounts of metabolic debris, which consequently leads to autoimmunization and enhanced permeability of the blood–retinal barrier. AAbs that were made as a part of anti-cancer response are likely to be the cause of retinal degeneration, whereas others, generated against released antigens from damaged retina, contribute to the progression of retinopathy. Altogether, AAbs may trigger retinal degeneration and may also exacerbate the degenerative process in response to the release of sequestered antigens and influence disease progression.

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“…Abs against proteins involved in the glycolytic pathway, a-Enolase and Aldolase C, have been reported in sera of AIR patients. However, the expression of these proteins is not restricted to retina, and autoantibodies against them have been detected in various autoimmune diseases (5). One of the ARA most correlated with AIR is anti-recoverin Ab (6).…”

mentioning

confidence: 99%

Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy

Nikoopour

Lin

Sheskey

et al. 2019

The Journal of Immunology

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Autoimmune retinopathy (AIR) is a treatable condition that manifests in acute and progressive vision loss in patients. It has recently been determined that AIR is associated with an imbalance of T H 1 versus regulatory T cell immunity toward the retinal protein, recoverin. This study describes a new murine model to understand the immunopathology of AIR and its association with T cell responses toward recoverin. Immunization of C57BL/6 mice with recoverin resulted in ocular inflammation including infiltration of CD4 + and CD8 + T lymphocytes, B cells, and CD11b + Ly6C + inflammatory monocytes in the eyes. Production of IFN-g and IL-17 from T cells was exacerbated in IL-10 knockout (KO) mice and kinetics of disease development was accelerated. Infiltration of T cells and inflammatory monocytes into the eyes dramatically increased in recoverin-immunized IL-10 KO mice. An immunodominant peptide of recoverin, AG-16, was capable of inducing disease in IL-10 KO mice and resulted in expansion of AG-16 tetramer-specific CD4 + T cells in lymphoid organs and eyes. Adoptive transfer of recoverin-stimulated cells into naive mice was sufficient to induce AIR, and immunization of B cell-deficient mice led to a milder form of the disease. This model supports the hypothesis that recoverin-specific T cell responses are major drivers of AIR pathogenesis and that IL-10 is an important factor in protection.

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Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

Cited by 25 publications

References 126 publications

Beneath the Retinal Pigment Epithelium: Histopathologic Findings in Metastatic Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

Beneath the Retinal Pigment Epithelium: Histopathologic Findings in Metastatic Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

Are Anti-Retinal Autoantibodies a Cause or a Consequence of Retinal Degeneration in Autoimmune Retinopathies?

Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy

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