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

Hauck, Stefanie M.; Hofmaier, Florian; Dietter, Johannes; Swadzba, Margarete E.; Blindert, Marcel; Amann, Barbara; Behler, Jennifer; Kremmer, Elisabeth; Ueffing, Marius; Deeg, Cornelia A.

doi:10.1016/j.jprot.2012.04.052

Cited by 44 publications

(59 citation statements)

References 35 publications

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“…Surgical removal of the VH can lead to a considerable decrease in the frequency and severity of relapses, therefore vitreous composites are likely to contribute to disease progression [52]. Deeg and coworkers have been systematically comparing VH from healthy and disease-affected equine eyes by proteomic profiling [53, 54]. In an earlier study, they applied 2-DE-MALDI-TOF/MS, identifying a total of 42 proteins, 9 of which differentially expressed in ERU.…”

Section: Future Perspectives: Proteomics For Intravitreal Inflammamentioning

confidence: 99%

“…These are functionally related to immune response, inflammation, and maintenance of the blood-retinal barrier [52]. More recently, they identified ERU-related functional protein networks and affiliated molecular signalling pathways using LC-MS/MS-based label-free quantification followed by pathway enrichment analyses [54]. The increased sensitivity gained by omitting gel-based prefractionation resulted in overall detection of 119 different proteins.…”

Section: Future Perspectives: Proteomics For Intravitreal Inflammamentioning

confidence: 99%

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Proteomic Analyses of the Vitreous Humour

Angi

Kalirai

Coupland

et al. 2012

Mediators of Inflammation

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The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes. In the last decade, proteomics analyses have been performed to characterise the proteome of the human VH and explore networks of functionally related proteins, providing insight into the aetiology of diabetic retinopathy and proliferative vitreoretinopathy. Recent proteomic studies on the VH from animal models of autoimmune uveitis have identified new signalling pathways associated to autoimmune triggers and intravitreal inflammation. This paper aims to guide biological scientists through the different proteomic techniques that have been used to analyse the VH and present future perspectives for the study of intravitreal inflammation using proteomic analyses.

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Section: Future Perspectives: Proteomics For Intravitreal Inflammamentioning

confidence: 99%

Section: Future Perspectives: Proteomics For Intravitreal Inflammamentioning

confidence: 99%

Proteomic Analyses of the Vitreous Humour

Angi

Kalirai

Coupland

et al. 2012

Mediators of Inflammation

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“…In addition to its dispensable roles in the development of T cells and the immune system, mounting evidence has recently suggested that it is involved in the pathogenesis of many types of autoimmune diseases, including rheumatoid arthritis (RA), SLE, spondyloarthritis (PsA), and ankylosing spondylitis (AS) [12–17]. In SLE patients, aberrant Wnt/ β -catenin signaling was observed in both peripheral B and T cell fractions [18].…”

Section: Introductionmentioning

confidence: 99%

Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

Xue

Yang

et al. 2017

Journal of Immunology Research

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An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p < 0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN.

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“…Acquired MS spectra were imported into Progenesis software (version 2.5 Nonlinear Dynamics, Waters and analyzed as previously described 42,43 . After alignment, peak picking, exclusion of features with charge of 1 and >7 and normalization, spectra were exported as Mascot Generic files and searched against the Ensembl Horse database (Version 78) with Mascot (Matrix Science, Version 2.4.1).…”

Section: Protein Identification and Label-free Quantificationmentioning

confidence: 99%

Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity

Schauer¹,

Kleinwort²,

Degroote³

et al. 2018

Preprint

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The GTP-binding protein septin 7 is involved in various cellular processes, including cytoskeleton organization, migration and the regulation of cell shape. Septin 7 function in lymphocytes, however, is poorly characterized. Since the intracellular signaling role of septin 7 is dependent on its interaction network, interaction proteomics was applied to attain novel knowledge about septin 7 function in hematopoietic cells. Our previous finding of decreased septin 7 expression in peripheral blood-derived lymphocytes in ERU, a spontaneous animal model for autoimmune uveitis in man, extended the role of septin 7 to a potential key player in autoimmunity. Here, we revealed novel insights into septin 7 function by identification of DOCK8 as an interaction partner in primary blood derived lymphocytes. Since DOCK8 is associated with important immune functions, our finding of significantly decreased DOCK8 expression and altered DOCK8 interaction network in ERU might explain changes in immune response and shows the contribution of DOCK8 in pathomechanisms of spontaneous autoimmune diseases. Moreover, our analyses revealed insights in DOCK8 function, by identifying the signal transducer ILK as a novel DOCK8 interactor in lymphocytes. Our finding of the enhanced enrichment of ILK in ERU cases indicates a deviant influence of DOCK8 on inter-and intracellular signaling in autoimmune disease.not peer-reviewed)

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

Cited by 44 publications

References 35 publications

Proteomic Analyses of the Vitreous Humour

Proteomic Analyses of the Vitreous Humour

Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity

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