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Grazyna Adamus, Sufang Yang; Distinctive Epitopes for Carbonic Anhydrase II Autoantibodies in Autoimmune Retinopathy and Cancer-Associated Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):489.
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© ARVO (1962-2015); The Authors (2016-present)
High titers of anti-carbonic anhydrase II (anti-CA II) autoantibodies were found in sera of patients with autoimmune retinopathies (AR), including cancer-associated retinopathy (CAR) and also in normal population. The goal of the study was to identify immunodominant epitopes for CAII and determine their association with AR and CAR, and examine a possible predictive value of anti-CAII autoantibodies.
A retrospective study was conducted on a cohort of 217 patients seropositive for human CAII. Autoantibody titers against CAII in monospecific sera of CAR, AR and normal controls were determined by ELISA. Epitope mapping was performed using 37 biotinylated synthetic peptides that overlapped the entire sequence of CAII. The peptides were coated onto a streptavidin-treated microplate and anti-CAII sera were tested for their ability to bind to immobilized peptides by ELISA. ANOVA test was used for statistical analysis.
We analyzed the prevalence of CAII major domains in normal and AR/CAR patients. The results revealed significant differences in epitope recognition between autoantibodies from different groups (p=0.009, two-way ANOVA). We demonstrated unique epitopes for anti-CAII autoantibodies of patients with cancer or without diagnosed cancer. Eighty six percent of AR sera predominantly reacted with the N-terminal peptide 85-90 (p<0.01), which corresponded to the catalytic core of the enzyme. The major epitope for CAR autoantibodies was found within the C-terminal peptide 218-222 (p<0.05) close the α-helix and it was specific for 69% patients. Anti-CAII autoantibodies from normal healthy subjects did not share the key determinants of either group of patients. We also discovered an epitope shift in antibody recognition from an AR epitope profile to the CAR profile (p<0.0001) in a male patient who presented with vision loss 2 years prior his diagnosis cancer. The analysis of epitope positions in 3D structure of the CAII revealed that the majority of responses depended on the surface-exposed residues.
The epitope mapping provided for the first time the main CAII epitope targets and suggested that differences in unique epitopes between AR and CAR depended on the origination of specific AAbs. The accurate distinction between AR and CAR antibodies offers new insight into the pathogenesis of retinal disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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