Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19

TNFA-308G>A and IL10-1082A>G polymorphisms seem to be predictive biomarkers of chronic HCV infection

This study was funded by the National Council for Scientifc and Technological Development (CNPQ #480128/2013-8) and by the Federal University of Pará (PROPESP/PAPQ/2020)Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. João de Barros Barreto Hospital. Belém, Pará, Brazil / Federal University of Pará. Institute of Health Sciences. School of Medicine. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, Pará, Brazil.Background: Genetic changes may induce dysregulated cytokine production and afect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-infammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis C. Method: The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classifcation) and HCV viral load. Results: The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and its absence could be associated with protection against HCV infection (p=0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p=0.0428). Neither polymorphism was associated with diferent levels of necroinfammatory activity or fbrosis scores. Conclusion: Our results suggest the polymorphic genotype at TNFA -308G>A as protective against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant associated with higher HCV viral load. Further studies must be performed in order to confrm these associations

Association of serum levels of C-reactive protein with CRP-717 T/C polymorphism and viremia in HCV and HBV carriers

Abstract INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response

Association of the <i>p75^NTR</i> Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p p p Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control

The Genetic Profile and Serum Level of IL-8 Are Associated with Chronic Hepatitis B and C Virus Infection

The present study evaluated the IL8-251 A/T polymorphism in samples from 74 patients with chronic hepatitis B (HBV), 100 patients with chronic hepatitis C (HCV), and 300 healthy donors (CG). The correlations of this polymorphism with plasma IL-8 and disease stage were calculated. Polymorphisms were identified by real-time PCR. IL-8 was measured by enzyme-linked immunosorbent assay. The IL8-251 A/T genotype was not associated with susceptibility to infection by HBV or HCV. The wild-type allele (A) was associated with higher levels of inflammation (p = 0.0464) and fibrosis scores (p = 0.0016) in the HBV group, representing an increased risk for increased inflammatory activity (OR = 1.84; p = 0.0464) and for high fibrosis scores (OR = 2.63; p = 0.0016). Viral load was higher in HBV patients with polymorphic genotypes (TA and TT) at the IL8-251 A/T polymorphism than in those with the wild-type genotype (p = 0.0272 and p = 0.0464, respectively). Plasma IL-8 was higher among patients infected with HBV or HCV than in the control group (p = 0.0445 and p = 0.0001, respectively). The polymorphic genotype was associated with lower IL-8 than the wild-type genotype in the HBV group (p = 0.0239) and the HCV group (p = 0.0372). The wild-type genotype for IL8-251 A/T and high IL-8 were associated with a worse prognosis for infections; therefore, they may contribute to viral persistence and the development of more severe forms of chronic viral liver diseases

The −3279C>A and −924A>G polymorphisms in the FOXP3 Gene Are Associated With Viral Load and Liver Enzyme Levels in Patients With Chronic Viral Liver Diseases

The transcription factor FOXP3 is an essential marker of the development and activation of regulatory T cells (Tregs), which are cells specialized in the regulation and normal tolerance of the immune response. In the context of chronic viral liver diseases, Tregs participate in the maintenance of infections by promoting histopathological control and favor the immune escape of viral agents by suppressing the antiviral response. Single nucleotide polymorphisms (SNPs) may influence the function of FOXP3 in a number of pathological conditions. The present study sought to evaluate the influence of SNPs in the FOXP3 gene promoter region in patients with chronic viral liver diseases. Three SNPs (−3279C&gt;A, −2383C&gt;T, and −924A&gt;G) were analyzed in groups of patients with chronic hepatitis C (CHC), active chronic hepatitis B (CHB-A), inactive chronic hepatitis B (CHB-I), and a healthy control group (CG) using real-time PCR. The frequencies of the polymorphic variants were compared between groups and correlated with liver histopathological characteristics and enzyme levels [i.e., alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)] obtained via biopsy and from the clinical records of the participating patients, respectively. For the −2338C&gt;T SNP, no significant differences were found in the frequencies of variants between groups or in the histological findings. Significant associations between the polymorphisms and the CHB-I group were not established. The −3279C&gt;A SNP was associated with altered viral loads (log10) and GGT levels in CHC patients with advanced stages of inflammatory activity and liver fibrosis. The −924A&gt;G SNP was associated with altered viral loads (log10) and liver enzyme levels among CHB-A patients with milder inflammation and fibrosis. However, the frequencies of the −3279C&gt;A and −924A&gt;G polymorphisms were not directly associated with the histopathological profiles of the analyzed patients. These polymorphic variants may influence hepatic function in patients with chronic viral liver diseases but are not directly associated with the establishment of the degree of inflammatory activity and liver fibrosis

The IL6-174G/C polymorphism associated with high levels of IL-6 contributes to HCV infection, but Is not related to HBV infection, in the Amazon Region of Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPQ (grants #480128/2013-8, #312979/2018-5, #301869/2017-0) and by the Federal University of Para (PROPESP/PAPQ/2021).Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, BrasilFederal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, BrazilFederal University of Pará. João de Barros Barreto University Hospital. Pathology Service. Belém, PA, Brazil / Federal University of Pará. Institute of Health Sciences. School of Medicine. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, BrazilThe dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence and progression of chronic hepatitis caused by HBV and HCV in 72 patients with chronic hepatitis B (HBV), 100 patients with hepatitis C (HCV), and a control group of 300 individuals. The genotyping of the IL6-174G/C polymorphism was performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). HCV patients with the wild-type genotype (GG) had a higher viral load (p = 0.0230). The plasma levels of IL-6 were higher among patients infected with HBV and HCV than among the control group (p &lt; 0.0001). Patients with HCV were associated with increased inflammatory activity (A2-A3; p &lt; 0.0001). In hepatitis C, carriers of the GG genotype had higher levels of IL-6 (p = 0.0286), which were associated with A2-A3 inflammatory activity (p = 0.0097). Patients with A2-A3 inflammatory activity and GG genotype had higher levels of IL-6 than those with the GC/CC genotype (p = 0.0127). In conclusion, the wild-type genotype for the IL6-174G/C polymorphism was associated with high levels of IL-6 and HCV viral load and inflammatory activity, suggesting that this genotype may be a contributing factor to virus-induced chronic infection

TREX1 531C&gt;T Polymorphism is Associated with High Proviral Load Levels in HTLV-1-Infected Persons

Human T-lymphotropic virus type 1 (HTLV-1) deregulates the immune system and cell cycle, resulting in loss of immune tolerance and disease, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Three prime repair exonuclease 1 (TREX1) maintains innate immune tolerance of the host and host-cell permissiveness to retroviral infections. TREX1 polymorphisms may influence the course of infection and autoimmune manifestations. The influence of TREX1 531C/T polymorphism was investigated in HTLV-1 infection and development of symptoms among 151 persons infected with HTLV-1 (32 HAM/TSP, 19 rheumatologic manifestations, two dermatitis, five more than one diagnosis, two probable HAM/TSP, and 91 asymptomatic individuals) and 100 uninfected persons in the control group. Polymorphism genotyping and proviral load quantification were performed by real-time polymerase chain reaction (PCR) and antinuclear antibodies (ANAs) were screened by an indirect immunofluorescence assay. No statistically significant difference was found in polymorphism genotype and allele frequencies between the infected and control groups. HAM/TSP patients showed higher frequency of TT genotype than asymptomatic persons (p = 0.0339). Proviral load was significantly higher among individuals with CT/TT genotypes and CC genotype carriers had lower proviral load and higher levels of proinflammatory cytokines. ANAs were present only in the HAM/TSP group. TREX1 531C&gt;T polymorphism seems to be associated with TREX-1 regulation and HTLV-1 infection

Intrahepatic interleukin 10 expression modulates fibrinogenesis during chronic HCV infection.

IntroductionLiver fibrosis is a result of continuous damage to the liver combined with accumulation of the extracellular matrix and is characteristic of most chronic liver diseases such as hepatitis C virus (HCV) infection.MethodsThis study evaluated interleukin 10 (IL10) expression in the liver and plasma of 45 HCV patients and its association with the pathogenesis and progression of liver fibrosis. The expression of transforming growth factor beta (TGFB1) was also assessed. Patients were divided into three groups according to the METAVIR classification (F0-F1, F2 and F3-F4); there was also a control group (n = 8).ResultsIn the control group, high intrahepatic IL10 mRNA expression showed a positive association with F0-F1 fibrosis, no inflammation, low concentrations of liver enzymes and a high viral load; conversely, low intrahepatic IL10 mRNA expression showed a negative association with fibrosis progression. Intrahepatic TGFB1 mRNA expression was greater in the HCV group than in the control group, and regarding different disease phases, its expression increased as fibrosis evolved to more severe forms.ConclusionIntrahepatic IL10 mRNA expression decreases with persistent fibrosis, probably due to the production of TGF-β1, a potent antimitotic and fibrogenic cytokine. IL10 restricts and decreases the immune response and limits the fibrogenic response; however, a decrease in IL10 favors persistent inflammatory infiltrate, resulting in severe fibrosis