2 research outputs found
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Expresión y activación de receptores intracelulares TLR7, TLR8 y TLR9 en monocitos de sangre periférica de pacientes infectados con VIH.
Introduction. TLR´s play a role in host defense in HIV infection
recognizing the viral DNA or RNA. Their activation induces a signaling
pathway that includes the proteins MyD88, IRAK4, TRAF6 and the
transcription factor NF-kBp65. Objective. To determine the expression
of TLR7, TLR8 and TLR9, and activation of its signaling pathway in
monocytes from patients infected with HIV. Methods. Expression of TLR7,
TLR8 and TLR9 was determined in monocytes from HIV-infected patients (n
= 13) and control subjects (n = 13), which were activated with specific
ligands. The expression of MyD88 and NF-kBp65 were determined by flow
cytometry; IRAK4 and TRAF6 were studied by immunoblotting. Results. No
statistical difference was found in the expression of TLR7, 8 and 9 in
monocytes from patients compared to controls, but we observed the
non-significant increased expression of TLR9 in patients. The
activation showed no significant difference in the expression of MyD88
and NF-kBp65 in patients when compared to controls, but were decreased
in stimulated cells over non-stimulated cells. IRAK4 and TRAF6 were not
detected. Conclusions. No statistical difference was observed in the
expression of intracellular TLRs, MyD88 and NFkBp65 in monocytes from
patients compared to controls. This was probably due to effective
antiretroviral therapy being received at the time of study entry.
Additional studies are needed (ARTV) under controlled conditions that
include infected patients with and without ARVT, responders and non-
responders, and work with different cell populations.Introducción. En la infección por VIH los TLR juegan un papel
en la defensa del huésped al reconocer el ADN o ARN viral. Su
activación induce la vía de señalización que
incluye las proteínas MyD88, IRAK4, TRAF6 y el factor de
transcripción NF-kBp65. Objetivo. Determinar la expresión del
TLR7, TLR8 y TLR9, y activación de su vía de
señalización en monocitos de pacientes infectados con VIH.
Métodos. Se determinó la expresión de TLR7, TLR8 y TLR9
en monocitos de pacientes infectados con VIH (n =13) y sujetos control
(n =13), se activaron con ligandos específicos y se determinó
la expresión de MyD88 y NF-kBp65 por citometría de flujo.
IRAK4 y TRAF6 fueron estudiadas por inmunoelectrotransferencia.
Resultados. No se observó diferencia estadística en la
expresión de TLR7, 8 y 9 en los monocitos de pacientes con
respecto a los controles, pero observamos aumento no significante del
TLR9 en los pacientes. La activación no mostró diferencia
significativa en la expresión de MyD88 y NF-kBp65 en pacientes con
respecto a los controles, pero se encontraron disminuidas en
células estimuladas con respecto a las no estimuladas. IRAK4 y
TRAF6 no se detectaron. Conclusiones. No se observó diferencia en
la expresión de los TLR, ni en la expresión de MyD88 y
NFkBp65, en monocitos de pacientes con respecto a los controles
probablemente debido a la terapia antirretroviral recibida al momento
del estudio. Se sugieren estudios con pacientes con y sin TARV,
respondedores y no respondedores, y trabajar con diferentes poblaciones
celulares