RESUMO
Background: Liver fibrosis is a leading cause of morbimortality in people with HIV/hepatitis C virus (HCV). Natural killer (NK) cells are linked with amelioration of liver fibrosis; however, NK cells from individuals coinfected with HIV/HCV with cirrhosis display impaired functionality and high PD-1 expression. Here, we aimed to study PD-1, TIGIT, and Tim3 as potential exhaustion markers in NK cells from persons coinfected with HIV/HCV with mild and advanced liver fibrosis. We also evaluated the role of PD-1 expression on NK cells after HCV clearance by direct-acting antivirals (DAAs). Methods: Peripheral blood mononuclear cells were isolated from individuals coinfected with HIV/HCV (N = 54; METAVIR F0/F1, n = 27; F4, evaluated by transient elastography, n = 27). In 26 participants, samples were collected before, at the end of, and 12 months after successful DAA treatment. The frequency, immunophenotype (PD-1, TIGIT, and Tim3 expression), and degranulation capacity (CD107a assay) of NK cells were determined by flow cytometry. Results: Unlike PD-1, Tim3 and TIGIT were comparably expressed between persons with mild and advanced fibrosis. Degranulation capacity was diminished in NK/TIGIT+ cells in both fibrosis stages, while NK/PD-1+ cells showed a lower CD107a expression in cirrhotic cases. Twelve months after DAA treatment, those with advanced fibrosis showed an improved NK cell frequency and reduced NK/PD-1+ cell frequency but no changes in CD107a expression. In individuals with mild fibrosis, neither PD-1 nor NK cell frequency was modified, although the percentage of NK/CD107a+ cells was improved at 12 months posttreatment. Conclusions: Although DAA improved exhaustion and frequency of NK cells in cirrhotic cases, functionality was reverted only in mild liver fibrosis, remarking the importance of an early DAA treatment.
RESUMO
La pandemia de COVID-19 ha puesto en jaque a los sistemas de salud en el mundo; la vinculación entre la investigación biomédica y la práctica asistencial ha probado ser un requisito fundamental para dar respuesta a la misma de manera eficiente y rápida. En este sentido, los biobancos se constituyen como un componente clave ya que favorecen el almacenamiento de grandes volúmenes de muestras biológicas gestionadas en base a criterios que garanticen su óptima calidad, armonización y seguridad, respetando requisitos éticos y legales que aseguran los derechos de los ciudadanos. La cesión de estas muestras a distintos grupos de investigación promueve el desarrollo de nuevas herramientas diagnósticas y terapéuticas y vacunas. Frente a la llegada del SARS-CoV-2 a la Argentina, el Biobanco de Enfermedades Infecciosas estableció rápidamente la colección COVID-19 constituida por muestras de plasma, suero y células mononucleares de sangre periférica de personas cursando la enfermedad o recuperadas. En solo seis meses se enrolaron 825 donantes, lo que significa alrededor de 14.000 viales de material biológico almacenados y a disposición de los investigadores que lo soliciten. A tal efecto, se realizaron seis actos de cesión a diversos grupos pertenecientes a instituciones de investigación, mientras que tres se encuentran en evaluación. Las muestras cedidas han permitido, por ejemplo, el desarrollo de kits serológicos de producción nacional; lo que pone de manifiesto que el rápido establecimiento de esta colección, bajo un sistema de gestión eficiente, constituye una herramienta muy valiosa en la respuesta a esta nueva enfermedad
The COVID-19 pandemic has driven an unprecedented health crisis. Cooperation between biomedical research and healthcare practice has been shown to be a fundamental requirement to provide an efficient and timely response. In this regard, biobanks are key components since they allow the storage of large volumes of biological samples with guaranteed optimum quality, harmonization and safety, ensuring ethical and legal requirements which protect citizen rights. The transfer of these samples to different research groups fosters the development of new diagnostic and therapeutic tools as well as vaccines. Upon SARS-CoV-2 arrival to Argentina, the Biobank of Infectious Diseases rapidly established the COVID-19 collection comprised by plasma, serum and peripheral blood mononuclear cells samples obtained from people within the acute phase of the infection or who have already recovered. In only 6 months, 825 donors were enrolled, representing around 14,000 vials of biological material stored and available to researchers who might require it. In this line, 6 transfer agreements have been already performed to different groups belonging to national research institutions, while 3 are under evaluation. The transferred samples have allowed, for instance, the development of nationally produced serologic kits, which shows that the rapid establishment of this collection, under an efficient management system, represents a highly valuable tool in the response to this new disease.