CRALBP is a Highly Prevalent Autoantigen for Human Autoimmune Uveitis

Cornelia A Deeg,Stephan R Thurau,Barbara Amann,Gerhild Wildner,Marius Ueffing,Stefanie M Hauck,Manfred Stangassinger,John W Crabb,Albert J Raith

doi:10.1155/2007/39245

Abstract

Cellular retinaldehyde binding protein (CRALBP) is an autoantigen in spontaneous equine recurrent uveitis. In order to test whether CRALBP contributes to human autoimmune uveitis, the specificity of antibodies from human uveitis patient's sera was first evaluated in two-dimensional (2D) Western blot analysis. Subsequent identification of the immunoreactive proteins by mass spectrometry resulted in the identification of CRALBP as a putative autoantigen. Additionally, sera from human uveitis and control patients were by Western blot using purified human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently () in human uveitis patients than in normal controls. Thirty out of 56 tested uveitis patient's sera contained autoantibodies reactive against CRALBP, compared to only four out of 23 normal control subjects. The presence of CRALBP autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible autoantigen in human autoimmune uveitis.

Highlights

Cellular retinaldehyde binding protein (CRALBP) was recently detected as major autoantigen in equine recurrent uveitis (ERU), a spontaneous model of human uveitis [1]
In order to test whether CRALBP contributes to human autoimmune uveitis, the specificity of antibodies from human uveitis patient’s sera was first evaluated in two-dimensional (2D) Western blot analysis
Autoantibody profiling led to identification of CRALBP as a novel uveitis autoantigen in horses with spontaneous equine recurrent uveitis (ERU) [1]

Summary

Introduction

Cellular retinaldehyde binding protein (CRALBP) was recently detected as major autoantigen in equine recurrent uveitis (ERU), a spontaneous model of human uveitis [1]. To the two other major uveitis autoantigens, Santigen (S-Ag) [2], and interphotoreceptor retinoid binding protein (IRBP) [3], CRALBP is expressed in both the retina and the pineal gland. The protein is expressed abundantly in RPE cells, where many reactions of the rod visual cycle take place. It is found in Mueller glial cells, which have been implicated in cone visual pigment regeneration [4]. In addition to the RPE and Mueller glial cells of the retina, CRALBP expression has been reported in the ciliary body, cornea, pineal gland, optic nerve, brain, and the iris [4]. Mutations in the CRALBP gene have been associated with several autosomal recessive retinal pathologies, including retinitis pigmentosa, retinitis punctata albescens, bothnia dystrophy, fundus albipunctatus, and in the newfoundland rod/cone dystrophy [4, 6]

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