Title | Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Velez, Gabriel, C Roybal Nathaniel, Colgan Diana, Tsang Stephen H., Bassuk Alexander G., and Mahajan Vinit B. |
Journal | JAMA Ophthalmol |
Volume | 134 |
Issue | 4 |
Pagination | 444-8 |
Date Published | 2016 Apr |
ISSN | 2168-6173 |
Keywords | Adrenal Cortex Hormones, Adult, Analysis of Variance, Case-Control Studies, Cytokines, Follow-Up Studies, Humans, Immunosuppressive Agents, Male, Middle Aged, Precision Medicine, Proteomics, Reference Values, Risk Assessment, Severity of Illness Index, Treatment Outcome, Uveitis, Visual Acuity |
Abstract | 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 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. |
DOI | 10.1001/jamaophthalmol.2015.5934 |
Alternate Journal | JAMA Ophthalmol |
PubMed ID | 26848019 |
PubMed Central ID | PMC4833518 |
Grant List | R01EY018213 / EY / NEI NIH HHS / United States R01EY024698 / EY / NEI NIH HHS / United States R01 EY018213 / EY / NEI NIH HHS / United States 5P30EY019007 / EY / NEI NIH HHS / United States R01 EY016822 / EY / NEI NIH HHS / United States K08 EY020530 / EY / NEI NIH HHS / United States R01EY016822 / EY / NEI NIH HHS / United States 5P30CA013696 / CA / NCI NIH HHS / United States K08EY020530 / EY / NEI NIH HHS / United States R01 EY024698 / EY / NEI NIH HHS / United States P30 EY019007 / EY / NEI NIH HHS / United States P30 CA013696 / CA / NCI NIH HHS / United States T32GM007337 / GM / NIGMS NIH HHS / United States T32 GM007337 / GM / NIGMS NIH HHS / United States |