Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study
BackgroundUnderstanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association betwe...
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Frontiers Media S.A.
2024-10-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1341612/full |
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| author | Rubén Martín-Escolano Rubén Martín-Escolano Ana Virseda-Berdices Ana Virseda-Berdices Juan Berenguer Juan Berenguer Juan Berenguer Juan González-García Juan González-García Juan González-García Oscar Brochado-Kith Oscar Brochado-Kith Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez Cristina Díez Cristina Díez Cristina Díez Victor Hontañon Victor Hontañon Victor Hontañon The Marathon Study Group Salvador Resino Salvador Resino María Ángeles Jiménez-Sousa María Ángeles Jiménez-Sousa A. Arranz F. Arnalich J. R. Arribas E. Aznar T. Aldamiz-Echevarría J. Bermejo J. Berenguer J. M. Bellón I. Bernardino M. J. Bustinduy A. Carrero S. Carretero E. Casas J. L. Casado M. Crespo P. Crespo C. Díez M. Díaz J. de Miguel F. Dronda H. Esteban C. Fanciulli A. Ferrer M. J. Galindo J. González-García I. Gutiérrez . A. Iribarren V. Hontañón C. López P. Miralles M. L. Montes A. Moreno S. Moreno L. Ortiz E. Ortega B Padilla J. F. Parras L. Pérez-Latorre F. Pascual M. Pérez M. J. Pérez-Elías J. M. Peña C. Quereda M. Ramírez E. Ribera J. F. Rodríguez-Arrondo J. Sanz J. Sanz I. Santos M. A. Sanfrutos S. Schroeder F. Tejerina M. J. Téllez E. Van den Eynde J. Vergas M. A. Von-Wichmann M. Yllescas J. F. Zamora |
| author_facet | Rubén Martín-Escolano Rubén Martín-Escolano Ana Virseda-Berdices Ana Virseda-Berdices Juan Berenguer Juan Berenguer Juan Berenguer Juan González-García Juan González-García Juan González-García Oscar Brochado-Kith Oscar Brochado-Kith Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez Cristina Díez Cristina Díez Cristina Díez Victor Hontañon Victor Hontañon Victor Hontañon The Marathon Study Group Salvador Resino Salvador Resino María Ángeles Jiménez-Sousa María Ángeles Jiménez-Sousa A. Arranz F. Arnalich J. R. Arribas E. Aznar T. Aldamiz-Echevarría J. Bermejo J. Berenguer J. M. Bellón I. Bernardino M. J. Bustinduy A. Carrero S. Carretero E. Casas J. L. Casado M. Crespo P. Crespo C. Díez M. Díaz J. de Miguel F. Dronda H. Esteban C. Fanciulli A. Ferrer M. J. Galindo J. González-García I. Gutiérrez . A. Iribarren V. Hontañón C. López P. Miralles M. L. Montes A. Moreno S. Moreno L. Ortiz E. Ortega B Padilla J. F. Parras L. Pérez-Latorre F. Pascual M. Pérez M. J. Pérez-Elías J. M. Peña C. Quereda M. Ramírez E. Ribera J. F. Rodríguez-Arrondo J. Sanz J. Sanz I. Santos M. A. Sanfrutos S. Schroeder F. Tejerina M. J. Téllez E. Van den Eynde J. Vergas M. A. Von-Wichmann M. Yllescas J. F. Zamora |
| author_sort | Rubén Martín-Escolano |
| collection | DOAJ |
| description | BackgroundUnderstanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection.MethodsWe performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index.ResultsDuring follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG.ConclusionWe discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment. |
| format | Article |
| id | doaj-art-172bda063f904417a50997f3f3bc0faf |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-172bda063f904417a50997f3f3bc0faf2025-08-20T02:11:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-10-011510.3389/fphar.2024.13416121341612Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective studyRubén Martín-Escolano0Rubén Martín-Escolano1Ana Virseda-Berdices2Ana Virseda-Berdices3Juan Berenguer4Juan Berenguer5Juan Berenguer6Juan González-García7Juan González-García8Juan González-García9Oscar Brochado-Kith10Oscar Brochado-Kith11Amanda Fernández-Rodríguez12Amanda Fernández-Rodríguez13Cristina Díez14Cristina Díez15Cristina Díez16Victor Hontañon17Victor Hontañon18Victor Hontañon19The Marathon Study GroupSalvador Resino20Salvador Resino21María Ángeles Jiménez-Sousa22María Ángeles Jiménez-Sousa23A. ArranzF. ArnalichJ. R. ArribasE. AznarT. Aldamiz-EchevarríaJ. BermejoJ. BerenguerJ. M. BellónI. BernardinoM. J. BustinduyA. CarreroS. CarreteroE. CasasJ. L. CasadoM. CrespoP. CrespoC. DíezM. DíazJ. de MiguelF. DrondaH. EstebanC. FanciulliA. FerrerM. J. GalindoJ. González-GarcíaI. Gutiérrez. A. IribarrenV. HontañónC. LópezP. MirallesM. L. MontesA. MorenoS. MorenoL. OrtizE. OrtegaB PadillaJ. F. ParrasL. Pérez-LatorreF. PascualM. PérezM. J. Pérez-ElíasJ. M. PeñaC. QueredaM. RamírezE. RiberaJ. F. Rodríguez-ArrondoJ. SanzJ. SanzI. SantosM. A. SanfrutosS. SchroederF. TejerinaM. J. TéllezE. Van den EyndeJ. VergasM. A. Von-WichmannM. YllescasJ. F. ZamoraCentro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainServicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainCentro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainServicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, SpainCentro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainBackgroundUnderstanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection.MethodsWe performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index.ResultsDuring follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG.ConclusionWe discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.https://www.frontiersin.org/articles/10.3389/fphar.2024.1341612/fullHIV/HCV-coinfectionHCV therapyimmune checkpoint proteinstype 2 diabetes mellitusdyslipidemiaTyG index |
| spellingShingle | Rubén Martín-Escolano Rubén Martín-Escolano Ana Virseda-Berdices Ana Virseda-Berdices Juan Berenguer Juan Berenguer Juan Berenguer Juan González-García Juan González-García Juan González-García Oscar Brochado-Kith Oscar Brochado-Kith Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez Cristina Díez Cristina Díez Cristina Díez Victor Hontañon Victor Hontañon Victor Hontañon The Marathon Study Group Salvador Resino Salvador Resino María Ángeles Jiménez-Sousa María Ángeles Jiménez-Sousa A. Arranz F. Arnalich J. R. Arribas E. Aznar T. Aldamiz-Echevarría J. Bermejo J. Berenguer J. M. Bellón I. Bernardino M. J. Bustinduy A. Carrero S. Carretero E. Casas J. L. Casado M. Crespo P. Crespo C. Díez M. Díaz J. de Miguel F. Dronda H. Esteban C. Fanciulli A. Ferrer M. J. Galindo J. González-García I. Gutiérrez . A. Iribarren V. Hontañón C. López P. Miralles M. L. Montes A. Moreno S. Moreno L. Ortiz E. Ortega B Padilla J. F. Parras L. Pérez-Latorre F. Pascual M. Pérez M. J. Pérez-Elías J. M. Peña C. Quereda M. Ramírez E. Ribera J. F. Rodríguez-Arrondo J. Sanz J. Sanz I. Santos M. A. Sanfrutos S. Schroeder F. Tejerina M. J. Téllez E. Van den Eynde J. Vergas M. A. Von-Wichmann M. Yllescas J. F. Zamora Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study Frontiers in Pharmacology HIV/HCV-coinfection HCV therapy immune checkpoint proteins type 2 diabetes mellitus dyslipidemia TyG index |
| title | Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study |
| title_full | Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study |
| title_fullStr | Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study |
| title_full_unstemmed | Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study |
| title_short | Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study |
| title_sort | low plasma levels of btla and lag 3 before hcv therapy are associated with metabolic disorders after hcv eradication in persons with hiv hcv coinfection a retrospective study |
| topic | HIV/HCV-coinfection HCV therapy immune checkpoint proteins type 2 diabetes mellitus dyslipidemia TyG index |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1341612/full |
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lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT clopez lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT pmiralles lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT mlmontes lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT amoreno lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT smoreno lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT lortiz lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT eortega lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT bpadilla lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jfparras lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT lperezlatorre lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT fpascual lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT mperez lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT mjperezelias lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jmpena lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT cquereda lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT mramirez lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT eribera lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jfrodriguezarrondo lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jsanz lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jsanz lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT isantos lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT masanfrutos lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT sschroeder lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT ftejerina lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT mjtellez lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT evandeneynde lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jvergas lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT mavonwichmann lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT myllescas lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy AT jfzamora lowplasmalevelsofbtlaandlag3beforehcvtherapyareassociatedwithmetabolicdisordersafterhcveradicationinpersonswithhivhcvcoinfectionaretrospectivestudy |