DEFB1 polymorphisms and HIV-1 mother-to-child transmission in Zambian population

6Human Beta Defensin-1 (hBD-1) is a component of the innate immune system, the first line of defence against pathogens, already reported as involved in the susceptibility to HIV-1 infection and HIV-1 mother-to-child transmission (MTCT) in different populations. We investigated the role of DEFB1 gene (encoding for hBD-1) functional polymorphisms in the susceptibility to HIV-1 MTCT in a population from Zambia.partially_openembargoed_20190320Zupin, Luisa; Polesello, Vania; Segat, Ludovica; Kamada, Anselmo Jiro; Kuhn, Louise; Crovella, SergioZupin, Luisa; Polesello, Vania; Segat, Ludovica; Kamada, Anselmo Jiro; Kuhn, Louise; Crovella, Sergi

MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannosebinding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection

DEFB1 polymorphisms and salivary hBD-1 concentration in Oral Lichen Planus patients and healthy subjects

The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP

Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration

Human \u3b2-defensin 1 (hBD-1) is an antimicrobial peptide involved in epithelial defence of various tissues, also present in the saliva. Individual genetic variations within the DEFB1 gene, encoding for hBD-1, could influence gene expression and protein production

Candida Infections and Human Defensins

Candida species infections are an important worldwide health issue since they do not only affect immunocompromised patients but also healthy individuals. Indeed Candida spp. are present as commensal flora in the host human body but they can switch into a pathological form inducing cellular damage and disease. Among Candida strains, C. albicans is the most prevalent in both mucosal and systemic infections. The host developed different mechanisms of protection against Candida infections; specifically the immune system and the innate immune response are the first line of defence. Defensis are a group of antimicrobial peptides, components of the innate immunity, produced at mucosal level and known to be active against bacteria, virus but also fungi. Defensins are able to recognize the pathogens cell wall (different in composition from the human ones), and disrupt it through membrane permeabilization. Although the exact mechanisms of defensins anti-fungal action are not completely elucidated, the findings of the reviewed studies highlight the pivotal role of these peptides in the immune response against Candida infections

Interleukin-10 gene promoter polymorphisms in celiac patients from north-eastern Italy

Celiac disease is a complex chronic intestinal disorder driven by an immune response against the gliadin fraction of gluten: many factors are involved in the pathogenesis of the disease, and among these Interleukin-10 could play an important role. In the present study, the -1082A>G, -819T>C and -592A>C IL10 functional polymorphisms were analyzed in 565 celiac patients and 576 healthy controls from north-eastern Italy, stratified for HLA class II celiac disease risk haplotypes. No significant differences were observed for the three IL10 polymorphisms distribution between celiac patients and controls with the exception of a slightly increased risk for the -1082A allele in HLA-DQ8 male individuals. Although our findings suggest that the IL10 genetic variants analyzed do not have a major role in the susceptibility to the development of celiac disease in north-eastern Italian patients, we think that the possible involvement of IL10 gene in CD should deserve further investigation and that large-scale studies are recommended to confirm our findings

DEFB1 polymorphisms and susceptibility to recurrent tonsillitis in Italian children

Introduction: The tonsils are secondary lymphoid organs fundamental for immune system response against pathogens within the oral cavity. Tonsillitis refers to inflammation of the pharyngeal tonsils that may include the adenoids and the lingual tonsils and that can be acute, recurrent, and chronic. Viral or bacterial infections, as well as immunologic factors are the main trigger to tonsillitis and disease\u2019s chronicity: the host immune responses, especially the innate one, could play an important role in susceptibility to the disease. Objectives: The current study aims at investigating the role of functional polymorphisms in the 50UTR (c.-52G>A, c.-44G>C and c.-20G>A) of DEFB1 gene, encoding for the antimicrobial peptide human beta-defensin 1, in the predisposition to recurrent tonsillitis in children from North Eastern Italy. Results: No significant correlation was found between DEFB1 allele, genotype and haplotype frequencies and recurrent tonsillitis susceptibility with the exception of an increased risk to disease development in patients carrying DEFB1 rare haplotypes. Conclusion: Our results may suggest that DEFB1 polymorphisms alone may not influence pathology susceptibility, however they could possibly concur, together with other factors involved in the genetic control of innate immune system, in the predisposition towards recurrent tonsillitis

Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers

Background: Lactoferrin is a member of the innate immune system acting in the first line of defence against pathogens, and it is known for its antibacterial, antifungal and antiviral activity, including HIV-1. Two polymorphisms, T29A and R47K, in the exon 1 region of the LTF gene (encoding for the lactoferrin protein) were previously described as able to influence the lactoferrin antimicrobial function. Objectives: LTF T29A and R47K genetic variants were analysed in a Zambian population to unravel if these polymorphisms could play a role in HIV-1 mother-to-child HIV-1 transmission. Methods: LTF T29A and R47K polymorphisms were genotyped, using allelic specific fluorescent probes and real time PCR, in a population comprising 101 HIV-1 positive mothers and 333 children born to seropositive mothers. Results: Maternal LTF T29A A/A and A/G genotypes were found to be associated with decreased risk of HIV-1 MTCT, being more frequent among non-transmitter mothers respect to transmitter mothers. Conclusion: Our data suggested that maternal LTF genetic background contributes to the susceptibility to HIV-1 transmission from mother to new-borns

[PROVISIONAL] Perforin Gene PRF1 c.900C>T Polymorphism and HIV-1 Vertical Transmission

Abstract Perforin-1, component of the immune system, is able to control Human Immunodeficiency Virus-1 (HIV-1) replication and it could be involved in HIV-1 mother-to-child transmission (MTCT). This study aims at evaluating the role of c.900C>T PRF1 gene (encoding for perforin-1) polymorphism (rs885822) in HIV-1 MTCT. PRF1 c.900C>T polymorphism was genotyped in 331 children from Zambia using Taqman probe on Real Time PCR platform. PRF1 c.900C>T C/T genotype was more frequent amongst HIV-1 exposed but non-infected children than in HIV-1 positive cases and the results were confirmed among children infected during breastfeeding. PRF1 c.900C>T correlated with protection against HIV-1 MTCT, suggesting its role in HIV-1 vertical transmission