Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease
Open accessAbstract
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.
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Ocular tissues, including the retina, shed intracellular proteins into adjacent intraocular fluid compartments such as vitreous fluid.
“proteomic studies of the eye reveal that ocular tissues, including the retina, shed intracellular proteins into adjacent intraocular fluid compartments (e.g., the vitreous fluid; Fig. 1a)20,26–28.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [26]
Vitreous fluid makes up 80% of the human eye by volume.
“This tissue makes up 80% of the human eye by volume and sequesters both intracellular and extracellular proteins shed from the retina and adjacent tissues20,26–28.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [26]
Vitreous fluid biopsies exhibit high enough intracellular and extracellular protein content to serve as proxy biopsies for the retina.
“Biopsies of vitreous fluid exhibit high enough intracellular and extracellular protein content to serve as proxy biopsies for the retina and guide treatment of human disease20,26.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [26]
Vitreous fluid sequesters both intracellular and extracellular proteins shed from the retina and adjacent tissues.
“This tissue makes up 80% of the human eye by volume and sequesters both intracellular and extracellular proteins shed from the retina and adjacent tissues20,26–28.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [26]
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References 16 · Cited by 66
- Authors
- Velez, G., Roybal, C. N., Colgan, D., Tsang, S. H., Bassuk, A. G., & Mahajan, V. B.
- Affiliations
- University of Iowa (US)
- Columbia University (US)
- Corresponding author
- Mahajan, Vinit B.
- Venue
- JAMA Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-04-01
- Volume
- 134
- Issue
- 4
- Pages
- 444
- ISSN
- 2168-6165 (ISSN-L)
- PMC
- PMC4833518
- OpenAlex
- W2326035963
- Cited by
- 66
- References
- 16
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 11 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 3
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (P30EY019007, K08EY020530, R01EY016822, R01EY018213, R01EY024698)
- National Cancer Institute (P30CA013696)
- National Institute of General Medical Sciences (T32GM007337)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Keywords
- posterior uveitis, cytokine signature, IL-23, interleukin-1 receptor, interleukin-17 receptor, IGFBP-2, nerve growth factor, PDGFRβ, BMP4, stem cell factor, retinal autoimmunity, personalized treatment, proteomics
- MeSH terms
- Adrenal Cortex Hormones, Adult, Analysis of Variance, Follow-Up Studies, Humans, Immunosuppressive Agents, Male, Middle Aged, Reference Values, Severity of Illness Index, Uveitis, Visual Acuity, Case-Control Studies, Cytokines, Treatment Outcome, Risk Assessment, Proteomics, Precision Medicine
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