Louise E van Eekeren, Quirijn de Mast, Elise M G Meeder, Adriana Navas, Albert L Groenendijk, Marc J T Blaauw, Wilhelm A J W Vos, Nadira Vadaq, Jéssica C Dos Santos, Joost Rutten, Niels P Riksen, Jan van Lunzen, Gert Weijers, Mihai G Netea, André J A M van der Ven, Eric T T L Tjwa, Leo A B Joosten
{"title":"艾滋病病毒感染者肝脏脂肪变性和纤维化的血浆蛋白质组特征：一项横断面研究。","authors":"Louise E van Eekeren, Quirijn de Mast, Elise M G Meeder, Adriana Navas, Albert L Groenendijk, Marc J T Blaauw, Wilhelm A J W Vos, Nadira Vadaq, Jéssica C Dos Santos, Joost Rutten, Niels P Riksen, Jan van Lunzen, Gert Weijers, Mihai G Netea, André J A M van der Ven, Eric T T L Tjwa, Leo A B Joosten","doi":"10.1016/j.ebiom.2024.105407","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.</p><p><strong>Methods: </strong>We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP) ≥263 dB/m) and -fibrosis (liver stiffness measurement (LSM) ≥7.0 kPa). Plasma protein concentrations (n = 2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics were assessed, and analyses were stratified by BMI category. In addition, concentrations of 242 proteins were compared between individuals (\"controls\") with and without liver steatosis (ratio of methylene:methylene and water >5.6% on magnetic resonance spectroscopy) from a separate cohort (300-OB), all having a BMI >26 kg/m<sup>2</sup>.</p><p><strong>Findings: </strong>Steatosis and fibrosis were associated with 67/2367 (2.2%) and 17/2367 (0.7%) differentially expressed proteins (DEP), respectively, enriched in mostly metabolic pathways. Immunoglobulin superfamily member 9 (IGSF9) was amongst the top DEP associated with both steatosis and fibrosis. Stratifying by BMI revealed 8/2367 DEP associated with steatosis in lean- and 12/2367 DEP in overweight/obese individuals, with two shared DEP (IGSF9 and GHR). Conversely, protein signatures of overweight/obese PLHIV (32/242 DEP) and overweight/obese HIV-uninfected individuals (32/242 DEP) exhibited substantial overlap with 16 shared DEP. Notably, DEP correlated with HIV characteristics in lean individuals but not in overweight/obese PLHIV.</p><p><strong>Interpretation: </strong>Lean and overweight/obese PLHIV exhibit distinct proteomic signatures associated with liver steatosis, with the former being more strongly correlated with HIV-specific factors and ART. In addition, we identified a protein, IGSF9, strongly related to liver fibrosis and steatosis across BMI categories.</p><p><strong>Funding: </strong>The 2000HIV study is funded by ViiV Healthcare.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513669/pdf/","citationCount":"0","resultStr":"{\"title\":\"Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study.\",\"authors\":\"Louise E van Eekeren, Quirijn de Mast, Elise M G Meeder, Adriana Navas, Albert L Groenendijk, Marc J T Blaauw, Wilhelm A J W Vos, Nadira Vadaq, Jéssica C Dos Santos, Joost Rutten, Niels P Riksen, Jan van Lunzen, Gert Weijers, Mihai G Netea, André J A M van der Ven, Eric T T L Tjwa, Leo A B Joosten\",\"doi\":\"10.1016/j.ebiom.2024.105407\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.</p><p><strong>Methods: </strong>We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP) ≥263 dB/m) and -fibrosis (liver stiffness measurement (LSM) ≥7.0 kPa). Plasma protein concentrations (n = 2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics were assessed, and analyses were stratified by BMI category. 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Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study.
Background: Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.
Methods: We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP) ≥263 dB/m) and -fibrosis (liver stiffness measurement (LSM) ≥7.0 kPa). Plasma protein concentrations (n = 2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics were assessed, and analyses were stratified by BMI category. In addition, concentrations of 242 proteins were compared between individuals ("controls") with and without liver steatosis (ratio of methylene:methylene and water >5.6% on magnetic resonance spectroscopy) from a separate cohort (300-OB), all having a BMI >26 kg/m2.
Findings: Steatosis and fibrosis were associated with 67/2367 (2.2%) and 17/2367 (0.7%) differentially expressed proteins (DEP), respectively, enriched in mostly metabolic pathways. Immunoglobulin superfamily member 9 (IGSF9) was amongst the top DEP associated with both steatosis and fibrosis. Stratifying by BMI revealed 8/2367 DEP associated with steatosis in lean- and 12/2367 DEP in overweight/obese individuals, with two shared DEP (IGSF9 and GHR). Conversely, protein signatures of overweight/obese PLHIV (32/242 DEP) and overweight/obese HIV-uninfected individuals (32/242 DEP) exhibited substantial overlap with 16 shared DEP. Notably, DEP correlated with HIV characteristics in lean individuals but not in overweight/obese PLHIV.
Interpretation: Lean and overweight/obese PLHIV exhibit distinct proteomic signatures associated with liver steatosis, with the former being more strongly correlated with HIV-specific factors and ART. In addition, we identified a protein, IGSF9, strongly related to liver fibrosis and steatosis across BMI categories.
Funding: The 2000HIV study is funded by ViiV Healthcare.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍：
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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