Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis
IntroductionUveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III in...
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Frontiers Media S.A.
2025-04-01
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| author | Danielle Dias Munhoz Dennyson Leandro M. Fonseca Igor Salerno Filgueiras Haroldo Dutra Dias Helder I. Nakaya Igor Jurisica Igor Jurisica Igor Jurisica Hans D. Ochs Hans D. Ochs Lena F. Schimke Luiz Vicente Rizzo Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques |
| author_facet | Danielle Dias Munhoz Dennyson Leandro M. Fonseca Igor Salerno Filgueiras Haroldo Dutra Dias Helder I. Nakaya Igor Jurisica Igor Jurisica Igor Jurisica Hans D. Ochs Hans D. Ochs Lena F. Schimke Luiz Vicente Rizzo Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques |
| author_sort | Danielle Dias Munhoz |
| collection | DOAJ |
| description | IntroductionUveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.MethodsIn this study, we conducted an integrative systems biology analysis of blood transcriptome data from 169 non-infectious uveitis patients (56 isolated uveitis, 113 systemic disease-associated uveitis) and 82 healthy controls.ResultsModular co-expression analysis identified distinct cytokine signaling networks, emphasizing interleukin and interferon pathways. A meta-analysis revealed 110 differentially expressed genes (metaDEGs) in isolated uveitis and 91 in systemic disease-associated uveitis, predominantly linked to immune responses. The Interferome database confirmed a predominance of type I and II IFN signatures in both groups. Pathway enrichment analysis highlighted inflammatory responses, including cytokine production (IL-8, IL1-β, IFN-γ, β, and α) and toll-like receptor signaling (TLR4, TLR7, TLR8, CD180). Principal component analysis emphasized the IFN signature’s discriminative power, particularly in systemic disease-associated uveitis. Machine learning identified IFN-associated genes as robust predictors, while linear discriminant analysis pinpointed CCR2, CD180, GAPT, and PTGS2 as key risk factors in isolated uveitis and CA1, SIAH2, and PGS in systemic disease-associated uveitis.ConclusionThese findings highlight IFN-driven imune dysregulation and potential molecular targets for precision therapies in uveitis. |
| format | Article |
| id | doaj-art-ced2637ecfe8433fa7def2e688a86678 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-ced2637ecfe8433fa7def2e688a866782025-08-20T02:08:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15098051509805Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitisDanielle Dias Munhoz0Dennyson Leandro M. Fonseca1Igor Salerno Filgueiras2Haroldo Dutra Dias3Helder I. Nakaya4Igor Jurisica5Igor Jurisica6Igor Jurisica7Hans D. Ochs8Hans D. Ochs9Lena F. Schimke10Luiz Vicente Rizzo11Otavio Cabral-Marques12Otavio Cabral-Marques13Otavio Cabral-Marques14Otavio Cabral-Marques15Otavio Cabral-Marques16Otavio Cabral-Marques17Experimental Biology Laboratory Prof. Dr. Geraldo Medeiros-Neto, Hospital Israelita Albert Einsten, Sao Paulo, BrazilInterunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, BrazilDepartment of Neuroscience, Institute of Biomedical Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, BrazilExperimental Biology Laboratory Prof. Dr. Geraldo Medeiros-Neto, Hospital Israelita Albert Einsten, Sao Paulo, BrazilDivision of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, CanadaDepartments of Medical Biophysics and Computer Science, and Faculty of Dentistry, University of Toronto, Toronto, ON, CanadaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaDepartment of Pediatrics, University of Washington School of Medicine, Seattle, WA, United StatesSeattle Children’s Research Institute, Seattle, WA, United StatesDepartment of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, BrazilExperimental Biology Laboratory Prof. Dr. Geraldo Medeiros-Neto, Hospital Israelita Albert Einsten, Sao Paulo, BrazilInterunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil0Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network, (USERN), Sao Paulo, Brazil1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo (USP), Sao Paulo, Brazil2D’Or Institute for Research and Education (IDOR), São Paulo, Brazil3Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo, Sao Paulo, BrazilIntroductionUveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.MethodsIn this study, we conducted an integrative systems biology analysis of blood transcriptome data from 169 non-infectious uveitis patients (56 isolated uveitis, 113 systemic disease-associated uveitis) and 82 healthy controls.ResultsModular co-expression analysis identified distinct cytokine signaling networks, emphasizing interleukin and interferon pathways. A meta-analysis revealed 110 differentially expressed genes (metaDEGs) in isolated uveitis and 91 in systemic disease-associated uveitis, predominantly linked to immune responses. The Interferome database confirmed a predominance of type I and II IFN signatures in both groups. Pathway enrichment analysis highlighted inflammatory responses, including cytokine production (IL-8, IL1-β, IFN-γ, β, and α) and toll-like receptor signaling (TLR4, TLR7, TLR8, CD180). Principal component analysis emphasized the IFN signature’s discriminative power, particularly in systemic disease-associated uveitis. Machine learning identified IFN-associated genes as robust predictors, while linear discriminant analysis pinpointed CCR2, CD180, GAPT, and PTGS2 as key risk factors in isolated uveitis and CA1, SIAH2, and PGS in systemic disease-associated uveitis.ConclusionThese findings highlight IFN-driven imune dysregulation and potential molecular targets for precision therapies in uveitis.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1509805/fullnon-infectious uveitisblood transcriptomeinterferon-regulated genescytokinesintegrative analysis |
| spellingShingle | Danielle Dias Munhoz Dennyson Leandro M. Fonseca Igor Salerno Filgueiras Haroldo Dutra Dias Helder I. Nakaya Igor Jurisica Igor Jurisica Igor Jurisica Hans D. Ochs Hans D. Ochs Lena F. Schimke Luiz Vicente Rizzo Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis Frontiers in Immunology non-infectious uveitis blood transcriptome interferon-regulated genes cytokines integrative analysis |
| title | Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis |
| title_full | Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis |
| title_fullStr | Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis |
| title_full_unstemmed | Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis |
| title_short | Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis |
| title_sort | integrative immunology identified interferome signatures in uveitis and systemic disease associated uveitis |
| topic | non-infectious uveitis blood transcriptome interferon-regulated genes cytokines integrative analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1509805/full |
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