PURPOSE: Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. METHODS: Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). RESULTS: LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. CONCLUSIONS: A number of serum proteins identified by this immunoproteomic study of human glaucoma may represent diseased tissue-related antigens and serve as candidate biomarkers of glaucoma.
PURPOSE: Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. METHODS: Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). RESULTS: LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. CONCLUSIONS: A number of serum proteins identified by this immunoproteomic study of humanglaucoma may represent diseased tissue-related antigens and serve as candidate biomarkers of glaucoma.
Authors: Franz H Grus; Stephanie C Joachim; Kai Bruns; Karl J Lackner; Norbert Pfeiffer; Martin B Wax Journal: Invest Ophthalmol Vis Sci Date: 2006-03 Impact factor: 4.799
Authors: Stuart J McKinnon; Donna M Lehman; N Grace Tahzib; Nancy L Ransom; Herbert A Reitsamer; Peter Liston; Eric LaCasse; Qiuhong Li; Robert G Korneluk; William W Hauswirth Journal: Mol Ther Date: 2002-06 Impact factor: 11.454
Authors: Stephanie C Joachim; Oliver W Gramlich; Panagiotis Laspas; Heiko Schmid; Sabine Beck; Harald D von Pein; H Burkhard Dick; Norbert Pfeiffer; Franz H Grus Journal: PLoS One Date: 2012-07-26 Impact factor: 3.240
Authors: Tatjana S Sarenac Vulovic; Sladjana M Pavlovic; Vladimir Lj Jakovljevic; Katarina B Janicijevic; Nemanja S Zdravkovic Journal: Int J Ophthalmol Date: 2016-08-18 Impact factor: 1.779
Authors: Gözde Hondur; Emre Göktas; Xiangjun Yang; Lama Al-Aswad; James D Auran; Dana M Blumberg; George A Cioffi; Jeffrey M Liebmann; Leejee H Suh; Danielle Trief; Gülgün Tezel Journal: Invest Ophthalmol Vis Sci Date: 2017-08-01 Impact factor: 4.799
Authors: Laura P Cohen; Jessica Wong; Aliya Z Jiwani; Scott H Greenstein; Stacey C Brauner; Sherleen C Chen; Angela V Turalba; Teresa C Chen; Lucy Shen; Douglas J Rhee; Janey L Wiggs; Jae Hee Kang; Stephanie Loomis; Louis R Pasquale Journal: Digit J Ophthalmol Date: 2014-06-30