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.

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 TGFB1 -509C/T polymorphism and elevated TGF-ß1 levels are associated with chronic hepatitis C and cirrhosis.

The IFN-γ and TGF-ß1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-ß1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-ß1 (p = 0.0400). IFN-γ and TGF-ß1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-ß1, which inhibits IFN-γ production, contributing to the progression to cirrhosis.

Polymorphisms in the TGFB1 and FOXP3 genes are associated with the presence of antinuclear antibodies in chronic hepatitis C.

Chronic infection with Hepacivirus C (HCV) can lead to the occurrence of antinuclear antibodies (ANAs) and changes in cytokine profiles that can be similar to autoimmune diseases. The aim of the study was to identify polymorphisms in important mediators of the immune response in association with ANAs, which could contribute to the development of autoimmunity in hepatitis C. The study included 87 patients with chronic hepatitis C who were evaluated for the presence of ANA (indirect immunofluorescence) and for polymorphisms in the FOXP3, IFNG, IL6, IL8, IL10, MBL2, CRP, TGFΒ1 and TNFA genes (real-time PCR). Of the patients evaluated, 17 (19.54%) had ANA reactivity. The G allele of the FOXP3 rs2232365 polymorphism was more frequent in ANA-positive women (p = 0.0231; OR = 3,285). The C allele of the TGFΒ1 rs1800469 polymorphism was associated with ANA production (p = 0.0169; OR = 2.88). The results suggest that polymorphisms in genes related to immunological regulation may be associated with mechanisms that lead to the emergence of autoantibodies in the context of chronic Hepacivirus C infection.