PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Plasma Proteomic Markers of Interleukin-1β Pathway Associated With Incident Age-Related Macular Degeneration in Persons With Aids(Elsevier, 2025) Hunt, Peter W.; Olshen, Adam B.; Murad, Natalia; Ambayec, Gabrielle C.; Sezgin, Efe; Schneider, Michael F.; Jabs, Douglas A.Objective To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach. Design A nested case-control study (analysis 1) and nested cohort study (analysis 2). Participants Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA). Methods Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality. Main Outcome Measures Incident intermediate-stage AMD; incident cataract; and mortality. Results Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1 beta pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality. Conclusions Upregulation of the IL-1 beta pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1 beta pathway may provide a therapeutic avenue for treatment of AMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2025;5:100794 (c) 2025 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Article Genetic Factors Associated With Age-Related Macular Degeneration Modulating Plasma Inflammatory Biomarker Levels in Patients With Aids(Taylor & Francis inc, 2024) Sezgin, Efe; Schneider, Michael F.; Hunt, Peter W.; Beck-Engeser, Gabriele; Ambayac, Gabriele C.; Jabs, Douglas A.IntroductionPatients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS.Materials and MethodsCryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C x 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C x 3motif chemokine receptor 1 (CX3CR1).ResultsIn Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels.ConclusionsGenetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.