Annalisa Fabris

Association between HLA-G 3'UTR 14-bp polymorphism and HIV vertical transmission in Brazilian children.

Objectives:The aim of our study was to verify the possible association between an HLA-G 14-bp deletion/insertion polymorphism and perinatal HIV transmission in Brazilian children. Design:We analyzed the 14-bp deletion/insertion polymorphisms in seronegative (i.e., exposed uninfected, N = 71) and seropositive (exposed infected, N = 175) Brazilian children born from HIV-positive mothers and in healthy controls (n = 175). Methods:HLA-G 14-bp deletion/insertion polymorphism (rs16375) was detected by PCR amplification of the target sequence followed by agarose gel electrophoresis. All the samples were also analyzed by direct sequencing in order to validate the genotyping results. Results:HIV-exposed uninfected children showed significant differences in their allele and genotype frequencies of the HLA-G 14-bp polymorphism when compared to both seropositive children and healthy controls. The 14-bp-deleted (D) allele was more frequent in exposed uninfected children (79%) than in healthy controls (60%) and HIV-positive children (58%); the higher percentage of the D allele found in the exposed uninfected children with respect to HIV-positive individuals was significantly associated with a reduced risk of vertical transmission. This effect was ascribable to the presence of the D/D homozygous genotype. Conclusion:Our findings support the possible role for the HLA-G 14-bp deletion/insertion polymorphism in the HIV vertical transmission in Brazilian children. The presence of the D allele and D/D genotype is associated with a protective effect toward HIV perinatal infection.

MBL2 genetic screening in patients with recurrent vaginal infections

Problem  Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.

MBL2 and MASP2 gene polymorphisms in patients with hepatocellular carcinoma

Summary.  The pathogenesis of hepatocellular carcinoma (HCC) is not fully understood, but the majority of patients with HCC are associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Mannan‐binding lectin (MBL) is a collectin that can act directly as opsonine or activate MBL‐associated serine proteases (MASPs) thus initiating the antibody‐independent pathway of the complement system. In our study, we analysed two MBL2 and MASP2 functional polymorphisms (MBL2 allele A/0 and MASP2 D120G) as well as MASP2 polymorphism (Y371D) responsible for an amino acidic change in the protein in 215 HCC patients (HBV‐infected, HCV‐infected, HBV/HCV co‐infected and patients with HCC with no viral infection) and 164 healthy controls to give new insights regarding the role of these two molecules in HCC and viral infection pathogenesis. No significant association was found between MBL2 or MASP2 alleles or genotypes, neither comparing the total patients with HCC and healthy controls nor between the different groups of HCC subjects divided for type of viral infection. Also, dividing the total HCC patients group into low MBL producer (A0 and 00 genotypes) and normal producer (AA genotype) and comparing MASP2 polymorphisms in these two groups, no significant differences were found. Our data do not seem to suggest a role for MBL2 and MASP2 polymorphisms in HCC susceptibility either for HBV–HCV infection‐dependent HCC or for HCC raised as a consequence of exposure to different risk factors.

Five new OTOF gene mutations and auditory neuropathy

OBJECTIVE Purpose of this paper is to analyse OTOF gene in a series of subjects affected by auditory neuropathy. METHODS Four children showing mild to profound prelingual deafness, confirmed by the absence of a clear and detectable responses at auditory brainstem responses (ABR), associated with the presence of bilateral OAE, were enrolled in the study. RESULTS AND CONCLUSIONS Genetic analysis identified five new mutations (a nonsense, a small and a large deletion and two splicing site mutations), and one missense mutation (F1795C) previously described. These results further confirm the role of OTOF gene in auditory neuropathy. In the absence of a context of neurological syndrome, the combination of absent ABR and positive OAE responses should lead to an auditory neuropathy diagnosis and to a mutational screening in OTOF.

ORIGINAL ARTICLE: MBL2 Genetic Screening in Patients with Recurrent Vaginal Infections

Problem  Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.

Tag–single nucleotide polymorphism–based human leukocyte antigen genotyping in celiac disease patients from northeastern Italy

We genotyped celiac disease (CD)-associated haplotypes DQ2.5, DQ8, DQ2.2, and DQ7 in 1005 CD patients from North Eastern Italy using a Tag-single nucleotide polymorphism (SNPs) approach and real time PCR platform, checking the accuracy and reliability of the method and comparing it to traditional PCR-SSP. Only 14 of 2010 chromosomes analyzed (0.7%) showed discrepancies between the Tag-SNPs real-time polymerase chain reaction (PCR) method and the PCR-single-strand polymorphism (SSP) technique, indicating a high sensitivity and specificity (ranging from 0.987 to 1 and from 0.998 to 0.999, respectively) for tagging with respect to corresponding human leukocyte antigen (HLA) alleles identified by PCR-SSP. Moreover, the overall cost of the Tag-SNPs HLA typing method was low (3 to 4 €/sample instead of 35 to 70 €/sample with commercial kits), making it suitable for mass screenings. Hence, we believe that the Tag-SNPs HLA typing could be used to complement or replace classic HLA typing in at high-risk groups, for research purposes and eventually in population screening programs.

ORIGINAL ARTICLE: MBL2 Genetic Screening in Patients with Recurrent Vaginal Infections: MBL2 IN RECURRENT VAGINAL INFECTIONS

Problem  Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.