TREX1 531C/T Polymorphism and Autoantibodies Associated with the Immune Status of HIV-1-Infected Individuals.

Autoimmune diseases can develop during HIV-1 infection, mainly related to the individual's immune competence. The study investigated the association of the TREX1 531C/T polymorphism and antinuclear antibodies (ANA) in HIV-1 infection and the time of antiretroviral therapy (ART) used. Cross-sectional and longitudinal assessments were carried out in 150 individuals, divided into three groups: ART-naïve, 5 years and 10 years on ART; ART-naïve individuals were evaluated for 2 years after initiation of treatment. The individuals' blood samples were submitted to indirect immunofluorescence tests, real-time PCR and flow cytometry. The TREX1 531C/T polymorphism was associated with higher levels of TCD4+ lymphocytes and IFN-α in individuals with HIV-1. Individuals on ART had a higher frequency of ANA, higher levels of T CD4+ lymphocytes, a higher ratio of T CD4+/CD8+ lymphocytes and higher levels of IFN-α than therapy-naïve individuals (p < 0.05). The TREX1 531C/T polymorphism was associated with better maintenance of the immune status of individuals with HIV-1 and ANA with immune restoration in individuals on ART, indicating the need to identify individuals at risk of developing an autoimmune disease.

STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy.

BACKGROUND: The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. METHODS: This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. RESULTS: From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. CONCLUSIONS: ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING-cGAS pathway.

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

BACKGROUND: Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory 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 classification) 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 different levels of necroinflammatory activity or fibrosis 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 confirm these associations.

Dynamics of anti-SARS-CoV-2 IgG antibodies post-COVID-19 in a Brazilian Amazon population.

BACKGROUND: In this study, the prevalence and persistence of anti-SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) IgG was evaluated in volunteers 90 days after COVID-19 (coronavirus disease 2019) diagnosis by correlating response dynamics with clinical conditions, epidemiological characteristics, and disease severity. METHODS: The study recruited 200 volunteers aged 18 years or older of both sexes diagnosed with COVID-19. Of the 200 volunteers initially selected, the 135 individuals who underwent serological testing for anti-SARS-CoV-2 antibodies on the first visit to the laboratory, were invited to return, after 90 days, and provide a new blood sample for a second assessment of the presence of anti-SARS-CoV-2 IgG antibody. Disease severity and longevity of symptoms were evaluated for each individual and associated with the serological profile. RESULTS: Among the 135 individuals who underwent a previous serological test for anti-SARS-CoV-2 antibody, 125 showed reactivity to IgG (92.6%). Of the 125 individuals with detectable IgG in the first test, 87 (69.6%) showed persistence of this antibody after 90 days and 38 (30.4%) lost IgG reactivity in the second evaluation. The frequency of all reported symptoms was higher in individuals who maintained IgG persistence after 90 days of symptoms. Symptom manifestations lasted ≥21 days in the group with a persistent IgG response (39.6%) and ≤ 7 days in the group with a nonpersistent IgG response (50.0%). The length of hospital stay and supplemental oxygen use were higher in individuals with a persistent IgG response. CONCLUSIONS: The results of the present study show a high frequency of loss of anti-SARS-CoV-2 IgG antibodies within 3 months after COVID-19 diagnosis in the Brazilian Amazon.

Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. METHODS: This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). CONCLUSIONS: Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.

NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon.

BACKGROUNDS: Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. METHODS: The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. RESULTS: The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. CONCLUSION: Mutations in the NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Immune escape mutations in HIV-1 controllers in the Brazilian Amazon region.

BACKGROUND: Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4+ T cells (CD4+TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4+TC levels without the use of antiretroviral therapy (ART). METHODS: The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4+TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations. RESULTS: Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations. CONCLUSION: The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.

HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype.

The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

Lack of Association between Polymorphisms of the TLR4 Gene and Infection with the Hepatitis B and C Viruses.

Toll-like receptor 4 (TLR4) plays a crucial role in the early recognition of pathogenic microorganisms and provides an ideal model to investigate the consequences of genetic variation and susceptibility to diseases. The present study investigated the occurrence of the single nucleotide polymorphisms (SNPs) rs4986790 (A>G) and rs4986791 (C>T) in the TLR4 gene in chronic carriers of the hepatitis B (HBV) and C (HCV) viruses. A total of 420 blood samples were collected (HBV, 49; HCV, 72; and controls, 299) at the liver disease outpatient clinic of Hospital da Fundação Santa Casa de Misericórdia do Pará (FSCMPA). Genomic DNA extracted from leukocytes was subjected to real-time polymerase chain reaction (qPCR) analysis to identify the genetic profile of the participants. No significant differences were found in the allele and genotype frequencies between the infected participants and controls. No significant associations were found between the investigated polymorphisms and inflammatory activity, fibrosis, and the presence of cirrhosis; the same results were obtained in the haplotype analysis. The results showed a lack of association between the rs4986790 and rs4986791 SNPs and susceptibility to infection with HBV and HCV, as well as clinical and laboratory information of the patients.

The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals.

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.

Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.

Evaluation of Feline Permanent Canine Tooth Mineral Density Using Micro-Computed Tomography.

The tooth is made up of three mineralized tissues, enamel, dentin, and cementum, which surround a non-mineralized tissue called the dental pulp. Micro-computed tomography (mCT) is an imaging technology based on X-rays that allows non-invasive visualization of objects at a microscopic scale, according to their radiopacity and in three dimensions (3D). Likewise, it allows the subsequent execution of morphological and quantitative analysis of the objects, such as, for example, the determination of the relative mineral density (MD). The present work aimed to describe the MD of feline teeth using mCT. The studied sample consisted of four European Shorthair cats, from which nine canine teeth were extracted per medical indication. These teeth were evaluated through dental radiography before and after their extraction. Using mCT and the CTAn software, the values of the relative mineral density of the root of each tooth and of specific segments corresponding to the coronal, middle, and apical thirds of the root were determined. Mean MD of root tissues was 1.374 ± 0040 g·cm-3, and of hard root, tissues was 1.402 ± 0.035 g·cm-3. Through mCT, it was possible to determine the mean MD values of feline canine teeth. The study of MD could become an ancillary method for the diagnosis and characterization of dental pathology.

Low levels of TNFA gene expression seem to favor the development of pulmonary tuberculosis in a population from the Brazilian Amazon.

TNF-α is a Th1 cytokine profile active in the control of Mycobacterium tuberculosis infection, IL-10 is associated with persistence of bacterial infection. The aim of the study was to investigate the association of TNFA -308G/A and IL10 -819C/T polymorphisms and TNFA and IL10 gene expression levels with pulmonary and extrapulmonary tuberculosis (n = 200) and control (n = 200). The individuals were submitted to genotyping and quantification of gene expression performed by real-time quantitative polymerase chain reaction (qPCR). No association was observed between the frequencies of polymorphisms evaluated and pulmonary tuberculosis. The frequency of polymorphic genotypes for TNFA -308G/A were associated with the extrapulmonary tuberculosis (p = 0.0445). The levels of TNFA expression were lower in the pulmonary tuberculosis group than in the control (p = 0.0009). There was a positive correlation between the levels of TNFA and IL10 in patients with pulmonary tuberculosis (r = 0.560; p = 0.0103). Reduced levels of TNFA expression may promote the formation of an anti-inflammatory microenvironment, favoring the persistence of the bacillus in the host, contributing to the establishment of pulmonary tuberculosis.

Association of Cytokine Gene Polymorphisms and Their Impact on Active and Latent Tuberculosis in Brazil's Amazon Region.

Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

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.

Introduction: Mannose-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. Methods: Blood 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. Results: The 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. Discussion: The 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.

[Giant left atrial myxoma presenting as acute myocardial infarction]. / Enfarte agudo do miocárdio como forma de apresentação de mixoma gigante da aurícula esquerda.

Myxomas are the most common type of benign cardiac tumor. The most frequent clinical presentations are symptoms resulting from atrioventricular valve obstruction or systemic embolization. Coronary embolization is a rare, although real and potentially fatal, complication of cardiac myxomas. We present a case report and review of the literature on this disease association. A 57-year-old woman was admitted to our coronary care unit with a diagnosis of non-ST elevation acute myocardial infarction. Transthoracic echocardiography showed a large left atrial mass attached to the interatrial septum, coral-like and with a friable appearance, suggestive of myxoma. Coronary angiography revealed no significant lesions and the patient underwent surgical excision of the mass, which histological study showed to be compatible with myxoma. The postoperative period was uneventful and the patient is doing well, with no recurrence of myxoma.

Characteristics of Oral Corticosteroid Users Among Persons with Asthma on GINA Step 3 Therapy and Above: A Cross-Sectional Study in Portuguese Community Pharmacies.

Purpose: Oral corticosteroids (OCS) are frequently used in asthma management but have an important risk-profile. The aim of the study is to characterize and compare the sociodemographic and clinical characteristics, treatment regimen and asthma control between OCS users and non-users among the population of asthma patients (≥18 years) at GINA step 3 and above treated with a fixed combination of an inhaled corticosteroid and a long-acting beta-agonist (ICS/LABA). Methods: Cross-sectional study in Portuguese community pharmacies. Data was collected via paper-based interview delivered at the pharmacy (sociodemographic characteristics and asthma treatment regimen, namely ICS/LABA and OCS utilization), followed by a telephonic interview collecting smoking history, comorbidities, body mass index (BMI), history of exacerbations and asthma-related healthcare resource utilization (HCRU) in the previous 12 months, as well as asthma control using the Control of Allergic Rhinitis and Asthma Test (CARAT®). Results: A total of 347 patients recruited in 98 pharmacies were included in the analysis. Of those, 328 had completed both questionnaires. A quarter of the individuals reported OCS use in the previous 12 months (OCS users), either as add-on therapy (6%) or exacerbation treatment (19%). Patients were mostly females (72%), with an average age of 59.5 years (SD=15.4). OCS users were significantly older and reported more frequently having conjunctivitis (25.9% vs 15.0%), osteoporosis (25.9% vs 13.4%), arthritis (14.6% vs 6.9%), and gastrointestinal disease (16.1% vs 8.1%). OCS users also reported greater urgent HCRU: unscheduled consultations (33.3% vs 9.3%) and emergency department (ED) visits (32.1% vs 12.1%). Both groups presented poor disease control (85.2% of OCS users vs 72.9% of non-OCS users). Conclusion: These results highlight the burden of OCS therapy to asthma patients and the need to improve asthma management, by adopting OCS sparing strategies in this subgroup of patients.

Monitoring of SARS-CoV-2 Specific Antibodies after Vaccination.

Vaccination is considered the most important measure to control the COVID-19 pandemic. Extensive follow-up studies with distinct vaccines and populations are able to promote robust and reliable data to better understand the effectiveness of this pharmacologic strategy. In this sense, we present data regarding binding and neutralizing (achieved by surrogate ELISA assay) antibodies throughout time, from vaccinated and previously infected (PI) health care workers (HCW) in Portugal. We analyzed serum samples of 132 HCW, who were vaccinated and with previous SARS-CoV-2 infection. Samples were collected before vaccination (baseline, M1), at second dose vaccine uptake (M2), and 25-70 days (M3) and 150-210 days (M4) after the second dose for vaccinated individuals. The IgG (anti-RBD/S) antibody geometric mean titers found on vaccinated HCW at M2 (GM = 116.1 BAU/mL; CI: 92.3-146.1) were significantly higher than those found on PI HCW at recruitment (M1) (GM = 35.9 BAU/mL; CI:15.4-83.4), and the neutralizing antibodies (nAb) were similar between these groups, of 93.2 UI/mL (95% CI 73.2-118.5) vs. 84.1 UI/mL (95% CI 40.4-155.9), respectively. We detected around 10-fold higher IgG (anti-RBD/S) antibodies titers in M3 when compared with M2, with a slight but significant decrease in titers from 36 days after the second dose vaccine uptake. The increase of nAb titers was correlated with IgG (anti-RBD/S) antibodies titers; however, in contrast to IgG (anti-RBD/S) antibodies titers, we did not detect a decrease in the nAb titer 36 days after a second vaccine dose uptake. At M4, a decrease of 8-fold in binding IgG (anti-RBD/S) and nAb was observed. No significant differences in antibody titers were observed by sex, age or chronic diseases. Our results suggest that IgG (anti-RBD/S) antibodies titers and nAb titers could be correlated, but an ongoing follow up of the cohort is required to better understand this correlation, and the duration of the immune response.

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.

The 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 < 0.0001). Patients with HCV were associated with increased inflammatory activity (A2−A3; p < 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.

High prevalence of antinuclear antibodies in patients with chronic hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is a serious public health concern due to its high prevalence and mortality rate. In chronic infection, HCV may induce autoimmune responses through the production of autoantibodies, including antinuclear antibodies (ANA). METHODS: We assessed the presence of ANA by indirect immunofluorescence using HEp-2 cells in 89 patients with chronic hepatitis C. We also collected data on epidemiological variables; clinical characteristics; and biochemical, hematological, molecular, and histopathological information from the patients to assess the impact of the presence of ANA in those patients. RESULTS: The prevalence of ANA in the patients was 20.2%, which was significantly higher than that found in healthy controls (2%). However, there was no association of this marker with epidemiological, clinical-laboratory, molecular or histopathological characteristics of hepatitis C, although a slightly higher prevalence of ANA was detected in women and in patients infected with subgenotype 1a. In a specific analysis, chronic HCV patients with the "rods and rings" cytoplasmic pattern had higher degrees of hepatic fibrosis than did ANA-negative patients. CONCLUSIONS: The results confirm a greater predisposition to the presence of ANA in patients with HCV, which may be associated with a worse prognosis, especially in the presence of the "rods and rings" cytoplasmic pattern.