Luciano Pereira

TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro‐ and anti‐inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin‐10 (IL‐10) and the tumor necrosis factor alpha (TNF‐α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF‐α ‐308 G>A (rs1800629), IL‐10 ‐1082 G>A (rs1800896) and ‐819/‐592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real‐time PCR. Diplotypes associated with low IL‐10 production and the TNF‐α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL‐10 ‐819 (‐592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL‐10 and the TNF‐α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587–1595, 2016.

Association of hepatitis C virus infection and liver fibrosis severity with the variants alleles of MBL2 gene in a Brazilian population.

Mannose binding lectin (MBL) is a molecule of the innate immunity, which activates the complement system and modulates inflammation. We investigated the association of the polymorphisms in the exon 1 and promoter region of the MBL gene (MBL2) with the susceptibility to hepatitis C virus (HCV) infection and the degree of liver fibrosis in Brazilian patients chronically infected with HCV. The study was performed in 232 healthy control subjects and 186 patients, 157 of whom underwent liver biopsy after histopathology analysis and classification of fibrosis according to Metavir score. Exon 1 was genotyped by melting temperature assay and the promoter region by Taqman real-time polymerase chain reacation. The frequency of genotypes related to low production of MBL was higher in patients with HCV than in controls (p(c) = 0.0001, odds ratio = 3.52; confidence interval = 1.86-6.71). In addition, the frequency of variant haplotype, HYO was higher in patients with the severe fibrosis stage F4 (10.7%) than in patients with the mild/moderate fibrosis stage F1/F2 (3.4%), when compared with the HYA haplotype (p(c) = 0.04, odds ratio = 5.25, confidence interval = 1.11-23.62). We conclude that MBL variant alleles expressing low levels of MBL are associated with the susceptibility to HCV infection and that the inheritance of HYO haplotype could be associated with fibrosis severity.

Low IL10 serum levels as key factor for predicting the sustained virological response to IFNα/ribavirin in Brazilian patients with HCV carrying IL28B CT/TT genotype

PROPOSE IL28B polymorphisms rs12979860 CC genotype was associated to protection of HCV infection and sustained virological response (SVR) in HCV infected patients treated with pegIFNα/ribavirin (IFNα/RIB), however, this polymorphism frequency varies depending on genetic components. Studies with larger number of Brazilian individuals, determining IL28B polymorphisms is lacking. Regarding to treatment response, the levels of IL10 seem to influence response to IFNα/RIB therapy. Thus, the IL28B polymorphism frequency was investigated in health controls and infected HCV patients, as well as, in patients who reach SVR vs Non-SVR. Also, to gain insight into the interplay between IL28B genotypes, IL10 levels and therapy response, a subgroup of genotyped HCV patients SVR and Non-SVR were analyzed regarding the IL10 production. METHODS It was enrolled 487 HCV infected patients and 234 healthy individuals. Patients with response to IFNα/RIB were classified as SVR (n = 81) and Non-SVR (n = 123). TAQMAN probes were used for genotyping the SNP rs12979860, resulting in CC, CT or TT genotypes. In one hundred one patients, the levels IL10 were measured at week 4 of IFNα/RIB. RESULTS CC genotype was associated to SVR (p = 0.029) and its frequency was higher in healthy individuals vs patients (p = 0.02). Patients carrying CT/TT with IL10<10 pg/mL, had a chance of 2.72 to achieve SVR in multivariate model (p = 0.043). CONCLUSION CC genotype was associated to SVR and protection to HCV infection. Moreover, IL28B genotyping and IL10 serum levels could be further explored as a useful algorithm for identify the CT/TT SVR patients.

Clinical diagnosis and alternative surgical treatment of tetralogy of Fallot in a dog. A case report

Tetralogia de Fallot foi diagnosticada em uma femea Cocker Spaniel, de 30 meses de idade, por meio de exames fisico, radiografico, eletrocardiografico e ecocardiografico. A paciente foi submetida a correcao cirurgica paliativa, tecnica de Blalock-Taussig, e em avaliacao recente, 46 meses apos a cirurgia, apresentava-se sem qualquer manifestacao sintomatica de descompensacao cardiopulmonar.

MBL2 polymorphism and autoimmune markers: reconsidering the complexity of biological systems in the choice of controls

The study of mannose-binding lectin (MBL) in disease physiopathology represents a fascinating challenge. MBL has a broad role as recognition pattern molecule of innate immunity, activating the complement system, and acting as an ‘ante-antibody’ because it has a role in mammals during the lag period that is required to develop an antibody response against infectious agents. Additionally, MBL recognizes altered self-antigens, extending its role beyond a traditional host defense as it appears to play a role as a modulator of inflammation (Takahashi et al., 2006). Our interest on the study of MBL initiated in 1998, after a great epidemic of dengue in the city of Recife, Brazil. We hypothesized that individuals that had high MBL binding activity to mannan would be associated to dengue hemorrhagic fever (DHF) in comparison with dengue fever (DF). Using an ‘in house’ sandwich ELISA we observed higher binding activity of MBL in patients infected with dengue compared to the control group. Regarding the DHF vs. DF group it was observed a trend to higher MBL activity in DHF (Mann–Whitney, P = 0.07) (Moura, 1999). Since then, our group pursues to understand primarily the possible influence of MBL polymorphism or its serum levels alteration in infectious diseases (Moura, 2004; Segat et al., 2007; Miranda et al., 2009; Melo et al., 2009) and sickle cell anemia (Oliveira et al., 2009; Mendonça et al., 2010). Studies associating the polymorphism of the structural and promoter regions of MBL2 and infectious or autoimmune diseases show different results, which could be related to many factors; (i) the number of the