GCAP1, Rab6, and HSP27: Novel autoantibody targets in cancer-associated retinopathy and autoimmune retinopathy

Sufang Yang, Alexander Dizhoor, David Wilson, Grazyna Adamus

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients’ AAbs. Methods: Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A). Results: Among the cohort of 173 patients, only 68 had anti-recoverin AAbs and the remaining 105 reacted with 4 unique proteins, which were identified as a Rab6A, HSP27, GCAP1, and GCAP2. Confocal images from a double labeling study confirmed the reactivity of AAbs with different types of cells in human retina, consistent with the target protein’s respective cellular functions. Patients (62/173) had been diagnosed with various kinds of cancer, including 20% of patients who had anti-recoverin, 11% anti-Rab6A, and 5% anti-HSP27 AAbs. Only 50% of recoverin-seropositive patients had cancer and the individuals with anti-recoverin AAbs had a significantly higher likelihood to be diagnosed with cancer than patients with other anti-23-kDa AAbs. Conclusions: The newly discovered retinal autoantigens may be involved in pathogenicity of CAR and AR. The recognition of AAbs against various retinal proteins associated with autoimmune retinal degeneration broadens the group of proteins related with these entities. Translational Relevance: Patients with anti-recoverin, anti-GCAP1, anti-Rab6A, and anti-HSP27 AAbs represented diverse clinical phenotypes, so the presence of diseaseassociated AAbs provides important information for molecular diagnosis.

Original languageEnglish (US)
Article number1
JournalTranslational Vision Science and Technology
Volume5
Issue number3
DOIs
StatePublished - May 1 2016

Fingerprint

Ocular Paraneoplastic Syndromes
HSP27 Heat-Shock Proteins
Autoantibodies
Recoverin
Proteins
Guanylate Cyclase-Activating Proteins
Hot Temperature
Neoplasms
Retinal Degeneration
GTP Phosphohydrolases
Autoantigens
Fluorescence Microscopy
Confocal Microscopy
Confocal microscopy
Proteomics
Molecular mass
Virulence
Retina

Keywords

  • Autoimmune response/ disease
  • Cancer-associated retinopathy
  • Recoverin

ASJC Scopus subject areas

  • Ophthalmology
  • Biomedical Engineering

Cite this

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title = "GCAP1, Rab6, and HSP27: Novel autoantibody targets in cancer-associated retinopathy and autoimmune retinopathy",
abstract = "Purpose: Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients’ AAbs. Methods: Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A). Results: Among the cohort of 173 patients, only 68 had anti-recoverin AAbs and the remaining 105 reacted with 4 unique proteins, which were identified as a Rab6A, HSP27, GCAP1, and GCAP2. Confocal images from a double labeling study confirmed the reactivity of AAbs with different types of cells in human retina, consistent with the target protein’s respective cellular functions. Patients (62/173) had been diagnosed with various kinds of cancer, including 20{\%} of patients who had anti-recoverin, 11{\%} anti-Rab6A, and 5{\%} anti-HSP27 AAbs. Only 50{\%} of recoverin-seropositive patients had cancer and the individuals with anti-recoverin AAbs had a significantly higher likelihood to be diagnosed with cancer than patients with other anti-23-kDa AAbs. Conclusions: The newly discovered retinal autoantigens may be involved in pathogenicity of CAR and AR. The recognition of AAbs against various retinal proteins associated with autoimmune retinal degeneration broadens the group of proteins related with these entities. Translational Relevance: Patients with anti-recoverin, anti-GCAP1, anti-Rab6A, and anti-HSP27 AAbs represented diverse clinical phenotypes, so the presence of diseaseassociated AAbs provides important information for molecular diagnosis.",
keywords = "Autoimmune response/ disease, Cancer-associated retinopathy, Recoverin",
author = "Sufang Yang and Alexander Dizhoor and David Wilson and Grazyna Adamus",
year = "2016",
month = "5",
day = "1",
doi = "10.1167/tvst.5.3.1",
language = "English (US)",
volume = "5",
journal = "Translational Vision Science and Technology",
issn = "2164-2591",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
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TY - JOUR

T1 - GCAP1, Rab6, and HSP27

T2 - Novel autoantibody targets in cancer-associated retinopathy and autoimmune retinopathy

AU - Yang, Sufang

AU - Dizhoor, Alexander

AU - Wilson, David

AU - Adamus, Grazyna

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Purpose: Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients’ AAbs. Methods: Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A). Results: Among the cohort of 173 patients, only 68 had anti-recoverin AAbs and the remaining 105 reacted with 4 unique proteins, which were identified as a Rab6A, HSP27, GCAP1, and GCAP2. Confocal images from a double labeling study confirmed the reactivity of AAbs with different types of cells in human retina, consistent with the target protein’s respective cellular functions. Patients (62/173) had been diagnosed with various kinds of cancer, including 20% of patients who had anti-recoverin, 11% anti-Rab6A, and 5% anti-HSP27 AAbs. Only 50% of recoverin-seropositive patients had cancer and the individuals with anti-recoverin AAbs had a significantly higher likelihood to be diagnosed with cancer than patients with other anti-23-kDa AAbs. Conclusions: The newly discovered retinal autoantigens may be involved in pathogenicity of CAR and AR. The recognition of AAbs against various retinal proteins associated with autoimmune retinal degeneration broadens the group of proteins related with these entities. Translational Relevance: Patients with anti-recoverin, anti-GCAP1, anti-Rab6A, and anti-HSP27 AAbs represented diverse clinical phenotypes, so the presence of diseaseassociated AAbs provides important information for molecular diagnosis.

AB - Purpose: Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients’ AAbs. Methods: Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A). Results: Among the cohort of 173 patients, only 68 had anti-recoverin AAbs and the remaining 105 reacted with 4 unique proteins, which were identified as a Rab6A, HSP27, GCAP1, and GCAP2. Confocal images from a double labeling study confirmed the reactivity of AAbs with different types of cells in human retina, consistent with the target protein’s respective cellular functions. Patients (62/173) had been diagnosed with various kinds of cancer, including 20% of patients who had anti-recoverin, 11% anti-Rab6A, and 5% anti-HSP27 AAbs. Only 50% of recoverin-seropositive patients had cancer and the individuals with anti-recoverin AAbs had a significantly higher likelihood to be diagnosed with cancer than patients with other anti-23-kDa AAbs. Conclusions: The newly discovered retinal autoantigens may be involved in pathogenicity of CAR and AR. The recognition of AAbs against various retinal proteins associated with autoimmune retinal degeneration broadens the group of proteins related with these entities. Translational Relevance: Patients with anti-recoverin, anti-GCAP1, anti-Rab6A, and anti-HSP27 AAbs represented diverse clinical phenotypes, so the presence of diseaseassociated AAbs provides important information for molecular diagnosis.

KW - Autoimmune response/ disease

KW - Cancer-associated retinopathy

KW - Recoverin

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