Vitreal IgM Autoantibodies Target Neurofilament Medium in a Spontaneous Model of Autoimmune Uveitis

Abstract

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.

Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2

“…Further significantly enriched functional pathways were 'platelet degranulation and response to elevated platelet cytosolic Ca2 + ,' 'lipoprotein metabolism' and 'formation of the fibrin clot' (Table 1). This is in agreement with previous studies from our group that indicate both complement pathway upregulation of central C3 molecule in ERU [19], and the detection of high levels of classical plasma proteins albumin and Immunoglobulin in ERU vitreous samples [20].…”

“…Removal of ApoA1 slightly changed the output of the pathway enrichment analysis from upregulated proteins, but the majority of significantly enriched pathways are still centred around changes of classical plasma proteins (Table 1). It is still unclear, whether the appearance of plasma proteins in the ERU eye reflects break-down of the blood retinal barrier or is indicative of specific changes, like elevation and transfer of certain Ig isotypes into the eye as recently shown for neurofilament M specific IgM antibodies [20].…”

“…Two members of ECMreceptor interaction network were recently verified and characterized in ERU [21], namely osteopontin (SPP1), which is additionally associated with pathways 'integrins in angiogenesis, beta1 integrin cell surface interactions,' 'integrin cell surface interactions,' 'osteopontin-mediated events' and 'signaling by PDGF' ( Table 2). The second previously reported protein is fibronectin 1 [20] (FN1; also associated with five additional downregulated pathways, see Table 2). Both proteins are produced by retinal Müller glial cells (RMG), which lose neuroprotective abilities and develop an inflammatory phenotype in ERU [21,22].…”

Retinal Glycoprotein Enrichment by Concanavalin A Enabled Identification of Novel Membrane Autoantigen Synaptotagmin-1 in Equine Recurrent Uveitis

“…In ERU, a spontaneous model for human autoimmune uveitis, a highly effective workflow for identification and validation of autoantigens was established in the past [5], however, no membrane protein was identified as autoantigen to date. It became clear that while unfractionated retinal tissue was an excellent antigenic source in previous screening experiments [3], [4], answering more specific questions required a specific adaptation of the experimental reading frame. In this study, prefractionation of retinal tissue as autoantigenic source for Western blot screenings was tested as a potential solution for this problem and proved to be an elementary step in order to specifically examine protein subgroups for potential novel autoantigens.…”

“…Recently, we deciphered changed protein expression in innate immune cells of ERU affected individuals [2]. Another important area of application is the continuous search for autoantigens, where proteomic identification methods led to a gradual expansion of knowledge about the ERU autoantigen spectrum [3], [4].…”