4 research outputs found
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The TIGIT+ T regulatory cells subset associates with nosocomial infection and fatal outcome in COVID-19 patients under mechanical ventilation
Abstract:
The TIGIT+FOXP3+Treg subset (TIGIT+Tregs) exerts robust suppressive activity on cellular immunity and predisposes septic individuals to opportunistic infection. We hypothesized that TIGIT+Tregs could play an important role in intensifying the COVID-19 severity and hampering the defense against nosocomial infections during hospitalization. Herein we aimed to verify the association between the levels of the TIGIT+Tregs with the mechanical ventilation requirement, fatal outcome, and bacteremia during hospitalization. TIGIT+Tregs were immunophenotyped by flow cytometry from the peripheral blood of 72 unvaccinated hospitalized COVID-19 patients at admission from May 29th to August 6th, 2020. The patients were stratified during hospitalization according to their mechanical ventilation requirement and fatal outcome. COVID-19 resulted in a high prevalence of the TIGIT+Tregs at admission, which progressively increased in patients with mechanical ventilation needs and fatal outcomes. The prevalence of TIGIT+Tregs positively correlated with poor pulmonary function and higher plasma levels of LDH, HMGB1, FGL2, and TNF. The non-survivors presented higher plasma levels of IL-33, HMGB1, FGL2, IL-10, IL-6, and 5.54 times more bacteremia than survivors. Conclusions: The expansion of the TIGIT+Tregs in COVID-19 patients was associated with inflammation, lung dysfunction, bacteremia, and fatal outcome
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Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients
Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1ÎČ, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19
Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients
OBJECTIVE:
In the present study, we analyzed the possible association of inflammasome gene variants and expression to rheumatoid arthritis (RA)'s development and severity in the Brazilian population.
MATERIALS AND METHODS:
Thirteen single nucleotide polymorphisms within six inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1) as well as IL1B and IL18 genes in two different Brazilian populations (from Northeast and Southeast Brazil) were analyzed. We also evaluated inflammasome gene expression profile in resting and LPS\u2009+\u2009ATP-treated monocytes from RA patients and healthy individuals. For genetic association study, 218 patients and 307 healthy controls were genotyped. For gene expression study, inflammasome genes mRNA levels of 12 patients and ten healthy individuals were assessed by qPCR.
RESULTS:
Our results showed that rs10754558 NLRP3 and rs2043211 CARD8 polymorphisms are associated with RA development (p value\u2009=\u20090.044, OR\u2009=\u20091.77, statistical power\u2009=\u20090.999) and severity measured by Health Assessment Questionnaire (HAQ) (p value\u2009=\u20090.03), respectively. Gene expression analyses showed that RA patients display activation of CASP1, IL1B and IL1R genes independently of LPS + ATP activation. In LPS\u2009+\u2009ATP-treated monocytes, NLRP3 and NLRC4 expressions were also significantly higher in patients compared with controls.
CONCLUSIONS:
The first reported results in Brazilian populations support the role of inflammasome in the development of RA