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Brief Report
April 2016

Precision MedicinePersonalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease

Author Affiliations
  • 1Omics Laboratory, University of Iowa Carver College of Medicine, Iowa City
  • 2Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City
  • 3Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City
  • 4Barbara and Donald Jonas Laboratory of Stem Cells and Regenerative Medicine and Bernard and Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • 5Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York
  • 6Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City
JAMA Ophthalmol. 2016;134(4):444-448. doi:10.1001/jamaophthalmol.2015.5934

Importance  To better characterize posterior uveitis, vitreous samples from 15 patients were subjected to antibody arrays, and the expression levels of 200 human cytokines were evaluated. Expression was analyzed by 1-way analysis of variance (significance at P < .01), unsupervised cluster algorithm, and pathway analysis.

Observations  Unbiased clustering of patients, based on their cytokine expression profile, suggested that particular protein networks and molecular pathways are altered in various forms of uveitis. Expression of interleukin 23 (IL-23), IL-1 receptor I (IL-1RI), IL-17R, tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2), insulinlike growth factor–binding protein 2 (IGFBP-2), nerve growth factor (b-NGF), platelet-derived growth factor receptor β polypeptide (PDGFRb), bone morphogenic protein 4 (BMP-4), and stem cell factor (SCF) constituted a common cytokine signature in the vitreous of patients with uveitis. In 1 patient with progressive, idiopathic visual loss, this last-line analysis implicated retinal autoimmunity, a diagnosis that was validated when her serum sample was found to contain antibodies to S-arrestin, a retinal protein and potent cause of autoimmune retinal degeneration.

Conclusions and Relevance  The analysis identifies a common cytokine signature for posterior uveitis and guides the diagnosis of a patient with idiopathic uveitis. Personalized treatment reversed the visual loss, illustrating how proteomic tools may individualize therapy.