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Swadzba, M.E.* ; Hirmer, S.* ; Amann, B.* ; Hauck, S.M. ; Deeg, C.A.*

Vitreal IgM autoantibodies target neurofilament medium in a spontaneous model of autoimmune uveitis.

Invest. Ophthalmol. Vis. Sci. 53, 294-300 (2012)
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PURPOSE. Although the presence of IgG autoantibodies in the vitreous of spontaneous cases of equine recurrent uveitis (ERU) has been demonstrated, the potential role of IgM reactivities during ERU pathogenesis remains unexplored. The purpose of this study was to examine the presence of IgM autoantibodies in vitreous specimens of ERU-affected horses and to test their binding specificity to intraocularly expressed proteins. METHODS. To test IgM autoantibody responses to retinal tissue, vitreous samples of eye-healthy controls and ERU patients were analyzed via two-dimensional Western blot analysis with equine retinal tissue as an antigen source. A candidate protein, the peptide neurofilament medium (NF-M), was identified via mass spectrometry and validated via enzyme-linked immunosorbent assay. Immunohistochemistry for NF-M expression was performed on healthy and ERU-affected retinal sections. RESULTS. Whereas autoreactivity was never detected in the healthy vitreous samples, NF-M was specifically targeted by vitreal IgM autoantibodies in 44% of the ERU cases. Vitreal anti-NF-M IgG was detected in only 8% of the ERU samples, pointing to a persistent IgM response. In healthy horse retina, NF-M was located in the retinal ganglion cells and their processes, with additional staining in the outer plexiform layer. NF-M expression in ERU-affected retinas decreased considerably, and the remaining expression was limited to the nerve fiber layer. CONCLUSIONS. Intraocular anti NF-M IgM autoantibodies occur with high prevalence in vitreous of spontaneous autoimmune uveitis cases. The IgM dominated response may indicate a thymus-independent response to NF-M and merits further investigation in ERU, as well as in its human counterpart, autoimmune uveitis. ( Invest Ophthalmol Vis Sci. 2012; 53:294-300) DOI:10.1167/iovs.11-8734
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Publication type Article: Journal article
Document type Scientific Article
Keywords EQUINE RECURRENT UVEITIS; ELEVATED INTRAOCULAR-PRESSURE; CYTOSKELETON PROTEINS; AXONAL-TRANSPORT; TRIPLET PROTEINS; GANGLION-CELLS; ANTIBODIES; ANTIGENS; DISEASE; RETINA
Language english
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 0146-0404
e-ISSN 1552-5783
Journal Investigative Ophthalmology & Visual Science, IOVS
Quellenangaben Volume: 53, Issue: 1, Pages: 294-300 Article Number: , Supplement: ,
Publisher Association for Research in Vision and Ophthalmology (ARVO)
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505700-001
PubMed ID 22199250
DOI 10.1167/iovs.11-8734
WOS ID WOS:000302694500046
Scopus ID 84859221219
Erfassungsdatum 2012-07-23
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