Seroreactivity Against Aqueous-Soluble and Detergent-Soluble Retinal Proteins in Posterior Uveitis

Ko, Audrey C.; Brinton, Jason Philip; Mahajan, Vinit B.; Zimmerman, Bridget; Brinton, Gregory S.; Stone, Edwin M.; Folk, James C.; Mullins, Robert F.

doi:10.1001/archophthalmol.2011.65

Cited by 19 publications

(14 citation statements)

References 19 publications

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“…AAbs against four glycolytic enzymes: aldolase (ALDO), α-enolase (ENO1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and pyruvate kinase M2 (PKM2) are particularly prevalent in sera of patients with autoimmune retinopathies, including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR). Similar AAbs were also reported in autoimmune uveitis (22, 23). Although anti-enolase and other enzymes can be detected in low titers in some healthy individuals (from 0 to 10% depending on population studied), they were likely generated in response to common infections (18, 24).…”

Section: Introductionsupporting

confidence: 85%

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

Adamus

2017

Front. Immunol.

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Autoantibodies (AAbs) against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR)] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. AAbs against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation of AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but the retina may be without pathological consequence until a failure of the blood–retinal barrier function, which would then allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.

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Section: Introductionsupporting

confidence: 85%

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

Adamus

2017

Front. Immunol.

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“…3 Moreover, antiretinal antibodies are detectable in an array of systemic autoimmune disorders 29,30 and retinal degenerations, 8,31 as well as in healthy controls, 9,32 suggesting that their presence is not necessarily diagnostic. It is possible that the antiretinal antibodies detectable in AIR may not be pathogenic, but rather a result of retinal damage untied to the underlying etiology.…”

Section: Discussionmentioning

confidence: 99%

B Cell Anomalies in Autoimmune Retinopathy (AIR)

Stansky

Biancotto

Dagur

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeAutoimmune retinopathy (AIR) is a retinopathy associated with unexplained vision loss presumably linked to circulating antiretinal antibodies; currently, however, there are no standardized criteria regarding the diagnosis, treatment strategy, or pathogenesis of this disease. The importance of B-lymphocyte immunophenotyping in the classification of AIR is unknown.MethodsWe utilized 15-color multiparametric flow cytometry to identify aberrations in B cell subsets that may contribute to the pathophysiology of AIR. Luminex cytokine analysis was also performed on plasma samples from AIR patients.ResultsSignificant differences in AIR patients compared to individuals with other inflammatory conditions or healthy donors were found in the B cell memory compartment, including an increase in naïve B cells and a decrease in switched and unswitched memory B cells, which correlated with alterations in immunoglobulin secretion.ConclusionsThese findings suggest that the maturation process of B cells may be impaired and that B cell immunophenotyping may help in understanding disease process in AIR.

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“…29,30 Antiretinal antibodies have been reported in up to 42% of normal controls. 31 Proving the pathogenicity of these autoantibodies in various disease states is difficult, and requires rigorous scientific proof. A recent review has shown that to date there have been at least 17 different antiretinal antibodies described in patients with presumed AIR.…”

Section: Antiretinal Antibodies: Pathogenic Uncertaintiesmentioning

confidence: 99%