Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease.

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 < .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.

• Authors: Gabriel Velez, C Nathaniel Roybal, Diana Colgan, Stephen H Tsang, Alexander G Bassuk, Vinit B Mahajan
• Journal: JAMA ophthalmology (JAMA Ophthalmol) Vol. 134 Issue 4 Pg. 444-8 (Apr 2016) ISSN: 2168-6173 [Electronic] United States
• PMID: 26848019 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Cytokines
• Immunosuppressive Agents

Topics

• Adrenal Cortex Hormones (administration & dosage)
• Adult
• Analysis of Variance
• Case-Control Studies
• Cytokines (metabolism)
• Follow-Up Studies
• Humans
• Immunosuppressive Agents (administration & dosage)
• Male
• Middle Aged
• Precision Medicine (methods)
• Proteomics (methods)
• Reference Values
• Risk Assessment
• Severity of Illness Index
• Treatment Outcome
• Uveitis (diagnosis, drug therapy)
• Visual Acuity (drug effects)