Autoantibodies to transducin in a patient with melanoma-associated retinopathy

Potter, Michael J.; Adamus, Grażyna; Szabo, Shelagh M.; Lee, Rehwa; Mohaseb, Kam; Behn, Darren

doi:10.1016/s0002-9394(02)01431-9

Cited by 62 publications

(47 citation statements)

References 4 publications

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“…The term ‘autoimmune retinopathy’ has been proposed to encompass CAR, MAR and presumed npAIR [9]. Over the past two decades, further autoantibodies to novel retinal antigens have been characterized, including antibodies to α-enolase [10], transducin-β [11] and transducin-α [12]. The identification of multiple retinal autoantibodies has led to the concept that they may serve as molecular biomarkers for clinical phenotypes, including antirecoverin, anti-α-enolase and antitransducin retinopathies [12,13].…”

Section: History and Classificationmentioning

confidence: 99%

“…Some patients with MAR have been found to express a variety of autoantibodies against various proteins including transducin-β [11], rhodopsin [47], arrestin [48], a 35-kDa protein in Müller glial cells, a 22-kDa neuronal antigen, mitofilin, titin and COX [49]. Mitofilin is a mitochondrial protein anchored in the inner mitochondrial membrane, presumed to influence the morphological structure and function of mitochondria [49].…”

Section: Antigens and Antibodiesmentioning

confidence: 99%

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Autoimmune Retinopathy

Braithwaite

Vugler²,

Tufail

2012

Ophthalmologica

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Autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that primarily affect retinal photoreceptor function, and include cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR) and presumed non-paraneoplastic autoimmune retinopathy (npAIR). Autoimmune retinopathy typically presents in the fifth and sixth decades with rapidly progressive, bilateral, painless visual deterioration but an unremarkable fundus examination. CAR, MAR and npAIR have an overlapping clinical phenotype, and extensive investigation is required to exclude other causes of retinopathy, and to identify any occult malignancy, before a presumptive diagnosis can be made. Delayed diagnosis, and treatment initiation relatively late in the disease course, may contribute to the poor visual prognosis. Various treatments have been attempted, including systemic immunosuppression with steroid and steroid-sparing agents, intravenous immunoglobulin, and plasmapheresis, but these lack an evidence base. A variety of antiretinal antibodies have been identified in patients with autoimmune retinopathy, including antibodies to recoverin, α-enolase and transducin-α, but seronegative disease is also common. Clinical access to specialised serological investigation is very limited internationally, and this exacerbates the management challenge presented by patients with suspected autoimmune retinopathy. Several decades of experimental research have resulted in very considerable advances in our understanding of the pathophysiological mechanisms that may underlie autoimmune retinopathy. However, the precise triggers which result in loss of ocular immune privilege and sudden autoimmune attack on retinal cells have yet to be elucidated. This review summarizes the classification, investigation and management of autoimmune retinopathy, and considers the evolving concepts about its immunological aetiology.

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Section: History and Classificationmentioning

confidence: 99%

Section: Antigens and Antibodiesmentioning

confidence: 99%

Autoimmune Retinopathy

Braithwaite

Vugler²,

Tufail

2012

Ophthalmologica

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“…GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; IS (inner segments) and OS (outer segments) of photoreceptors; RPE, retinal pigment epithelium. ferent MAR patients have degenerations in distinct retinal cell types, (iii) sera of MAR patients stain different layers of the retina, and (iv) AA against 2 photoreceptor proteins, namely Rho 18 and Tr, 17 have been described in MAR patients. On the basis of these observations, we hypothesize that CRA may also be paraneoplastic antigens in MAR.…”

Section: Discussionmentioning

confidence: 99%

“…After positive PET/CT findings (12/1999 Additional sera were obtained from previously described MAR cases. 17,26 Patients MAR-2 and MAR-3 were male and suffered from night blindness, photopsias and problems with contrast sensitivity. Both patients had abnormal ERG and tritan defects on the FM 100-Hue test.…”

Section: Patientsmentioning

confidence: 99%

“…Sera of MAR patients appear to show reactivity against photoreceptor cells. 12 In addition, AA against two photoreceptor proteins, transducin (Tr) 17 and rhodopsin (Rho), 18 were found in the sera of patients with MAR. These data allow us to suggest that not only bipolar cells but also photoreceptor cells may be involved in the MAR syndrome (for review see Ref.…”

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confidence: 99%

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Cancer‐retina antigens as potential paraneoplastic antigens in melanoma‐associated retinopathy

Bazhin

Dalke

Willner

et al. 2008

Intl Journal of Cancer

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Melanoma-associated retinopathy is a rare paraneoplastic neurological syndrome characterized by retinopathy in melanoma patients. The main photoreceptor proteins have been found to be expressed as cancer-retina antigens in melanoma. Here we present evidence that these can function as paraneoplastic antigens in melanoma-associated retinopathy. Sera and one tumor cell line of such patients were studied and ret-transgenic mice spontaneously developing melanoma were used as a murine model for melanoma-associated retinopathy. Splenocytes and sera were used for adoptive transfer from tumor-bearing or control mice to wildtype mice. Retinopathy was investigated in mice by funduscopy, electroretinography and eye histology. Expression of photoreceptor proteins and autoantibodies against arrestin and transducin were detected in melanoma-associated retinopathy patients. In tumor-bearing ret-transgenic mice, retinopathy was frequently (13/ 15) detected by electroretinogram and eye histology. These pathological changes were manifested in degenerations of photoreceptors, bipolar cells and pigment epithelium as well as retinal detachment. Mostly these defects were combined. Cancer-retina antigens were expressed in tumors of these mice, and autoantibodies against arrestin were revealed in some of their sera. Adoptive transfer of splenocytes and sera from tumor-bearing into wildtype mice led to the induction of retinopathy in 4/16 animals. We suggest that melanoma-associated retinopathy can be mediated by humoral and/or cellular immune responses against a number of cancer-retina antigens which may function as paraneoplastic antigens in melanoma-associated retinopathy. '

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Autoantibodies Against Bestrophin in a Patient With Vitelliform Paraneoplastic Retinopathy and a Metastatic Choroidal Malignant Melanoma

Eksandh¹

2008

Arch Ophthalmol

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opmental glaucoma by monosomy 9p23 with trisomy 8q22. 2 The investigators attributed the responsible area of glaucoma to 8q22, not 9p23, because GLC1D maps to 8q22. That case also showed retained testis and hydronephrosis, similar to our patient. Interestingly, 2 previously reported cases 3,4 of monosomy 9p24-pter (near the 9p23 locus) manifested developmental glaucoma. Therefore, partial monosomy 9p might be causative for developmental glaucoma. Chromosome 13 seems essential for development of the eye. Trisomy 13 often results in severe ocular defects, including developmental glaucoma. 5 One case of developmental glaucoma and polydactyly with trisomy 13 was reported, 5 which is compatible with our case. In a French family with congenital microcoria, axial myopia, and juvenile open-angle glaucoma, genetic linkage to 13q31-32 was suggested to result in these ocular findings. 6 Although our patient had a normal pupil phenotype, trisomy 13q31 might be responsible for the developmental anomaly of angle. Taken together, it is suggested that the abnormalities of chromosome 9p23 and/or 13q31 are associated with developmental glaucoma with other systemic anomalies.

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Autoantibodies to transducin in a patient with melanoma-associated retinopathy

Cited by 62 publications

References 4 publications

Autoimmune Retinopathy

Autoimmune Retinopathy

Cancer‐retina antigens as potential paraneoplastic antigens in melanoma‐associated retinopathy

Autoantibodies Against Bestrophin in a Patient With Vitelliform Paraneoplastic Retinopathy and a Metastatic Choroidal Malignant Melanoma

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