ABSTRACT.Purpose: To determine the prevalence of serum antiretinal antibodies (ARAs) among patients with uveitis and establish their clinical relevance. Methods: This prospective study assessed the presence of ARAs by indirect immunofluorescence (IIF) using primate retina in 126 patients with uveitis and 60 healthy controls. Clinical data of uveitis patients were collected from medical charts and included the classification of uveitis, cause of uveitis or its association with systemic disease, stage and activity of uveitis and specific retinal features. Correlations between the presence of specific ARAs and various clinical characteristics were analysed. Results: The presence of ARAs was observed in 49 of 104 (47%) of patients with uveitis and in 10 of 59 (17%) of healthy controls (p < 0.001). Staining of the nuclear layers or the photoreceptors were both more often observed in patients with uveitis compared to healthy controls (p = 0.002 and p = 0.018, respectively). No specific associations were found between the presence of serum ARAs and various clinical characteristics. Conclusion: Serum ARAs were more frequent in patients with uveitis compared to healthy controls, but their clinical role remains elusive. The assessment of intraocular production of specific ARAs may provide further insight into the role of ocular autoantibodies in diverse uveitis entities.

PurposeAlthough multiple serum antiretinal autoantibodies (ARAs) have been reported in patients with paraneoplastic and non-paraneoplastic autoimmune retinopathy ((n)pAIR), not all retinal antigens involved in (n)pAIR are specified. This study aims to serologically identify patients with presumed (n)pAIR through determination of both known and unknown ARAs by autoantibody profiling.MethodsAn antigen suspension bead array using 188 different antigens representing 97 ocular proteins was performed to detect ARAs in serum samples of patients with presumed (n)pAIR (n = 24), uveitis (n = 151) and cataract (n = 21). Logistic regressions were used to estimate the associations between ocular antigens and diagnosis. Validation of interphotoreceptor matrix proteoglycan 2 (IMPG2) and recoverin antigens was performed by immunohistochemistry and immunoblot, respectively.ResultsSamples of patients with presumed (n)pAIR exhibited a broad spectrum of ARAs. We identified retinal antigens that have already been described previously (e.g. recoverin), but also identified novel ARA targets. Most ARAs were not specific for (n)pAIR since their presence was also observed in patients with cataract or uveitis. High titers of autoantibodies directed against photoreceptor-specific nuclear receptor and retinol-binding protein 3 were more common in patients with presumed (n)pAIR compared to uveitis (p = 0.015 and p = 0.018, respectively). The presence of all other ARAs did not significantly differ between groups. In patients with presumed (n)pAIR, anti-recoverin autoantibodies were the most prevalent ARAs. Validation of bead array results by immunohistochemistry (anti-IMPG2) and immunoblot (anti-recoverin) showed concordant results in (n)pAIR patients.ConclusionsPatients with (n)pAIR are characterized by the presence of a broad spectrum of ARAs. The diagnosis of (n)pAIR cannot be based on the mere presence of serum ARAs, as these are also commonly present in uveitis as well as in age-related cataract patients.

Serum ARAs are present in more than half of the patients with CSC, and especially, ARAs directed against photoreceptors were detected more frequently compared to both healthy controls and uveitis patients. Further research is warranted to unravel the role of ARAs in the pathogenesis of CSC.

No abstract