Abstract
Purpose: :
To identify auto antibodies against retinal pigment epithelium (RPE) in patients with various forms of putative autoimmune retinopathy and choroidopathy and to evaluate the potential biomarkers that will assist the diagnosis of specific retinal disorders or their complications.
Methods: :
Screening of auto antibodies in patient sera was performed by Western blotting using RPE cell extract. Indirect fluorescent immunocytochemistry was performed in cultured human primary RPE cells, using patient sera and fluorophorelabeled goat anti-human IgG. Proteins identified in immunoblotting were further differentiated by 2D electrophoresis and subjected to mass spectrometry; candidate proteins were validated with patient sera. Gene expression of patients RNA was assayed using theTH17 autoimmunity and inflammation arrays of 84 genes. Real time RT-PCR was employed to examine the inflammatory responses in some of the patients.
Results: :
We have screened anti-RPE antibodies in 106 patients(72 females,male,34 males) suffering various forms of auto immune retinopathy. We detected higher percentage of auto antibodies against RPE among patients with retinitis pigmentosa with cystoid macular edema (CME), occult foveal dystrophy, acute zonal occult outer retinopathy (AZOOR), and chorioretinitis ( 52% of patients under 60 years old vs. 22% of normal control.) These auto antibodies are against a variety of RPE components, with 55% stained the nuclei, 45% stained the cytoplasm, or both. A special group of patients had auto antibodies against the cytoskeleton (15%). More female patients (68%) carried anti RPE auto antibodies than male patients (32%). Anti RPE auto antibodies seemed increase with age, even in normal controls. Correlating these antibodies to pathologic effects has yet to be determined. Our results showed an increase in gene expression of the TH17 pathway in some patients.
Conclusions: :
Our findings indicate that elevated auto antibodies against RPE exist in some patients with various retinopathies and may contribute to causing some retinal disorders and vision impairment. Further investigation of autoimmune and inflammatory mechanisms in these patients, and identification of target proteins will continue to be carried out in our study.
Keywords: autoimmune disease • retinal pigment epithelium • clinical (human) or epidemiologic studies: prevalence/incidence