[Role of antibodies in kidney transplant]

Rejection is one of the most frequent causes of graft loss after a kidney transplant. In this context, in the last few years the essential role of antibodies in the anti-graft immune response has become more evident. Antibody-mediated damage has been classified into four histological patterns: hyperacute rejection, caused by the presence of pre-existing donor-specific antibodies directed against HLA or non-HLA antigens; acute antibody-mediated rejection, usually due to antibodies elicited following transplantation; chronic antibody-mediated rejection, which can develop months or years after the first appearance of circulating antibodies; and Cd4 deposition without morphologic evidence of active rejection, previously described as ''accommodation''. In recent years, thanks to the development of specific desensitization protocols, it has become possible to transplant patients sensitized to donor HLA antigens. Recently, besides consolidated protocols which include immunoglobulin administration associated or not with plasmapheresis, novel approaches of therapeutic apheresis with specific removal of antibodies and bortezomib, an agent that can efficiently decrease donor-specific antibody levels, have been developed. As far as the treatment of antibody-mediated rejection is concerned, different immunosuppressive strategies have been used. These include the combination of immunoglobulin administration and plasmapheresis with or without the use of an anti-CD20 monoclonal antibody. More recently, an innovative therapy with eculizumab has proved to be very effective against acute antibody-mediated rejection. The debate regarding the cause-effect relationship between the development of an early post-transplant humoral immune response in patients with stable graft function and premature graft loss remains open to discussion. Clinical studies are underway to provide an adequate answer to this question. In conclusion, comprehension of the fundamental role of antibodies and the consolidation of desensitization techniques together with early treatment of antibody-mediated rejection remain important objectives to improve long-term allograft survival

Epidemiology of Avian pathogenic Escherichia coli (APEC) in a finisching male turkey farm: longitudinal survey of three consecutive production cycles.

The purpose of this study was to investigate the epidemiology of APEC (Avian Pathogenic Escherichia coli), in a finishing male turkey commercial farm, conducting longitudinal surveys of three consecutive production cycles. The diversity and the distribution of APEC strains during the production cycles were examined using microbiological and molecular techniques. APEC isolates were serotyped, assessed for the presence of virulence-associated genes (pathogenic potential – pathotype) and for resistance to antibiotics (resistotype). Random Amplified Polymorphic DNA (RAPD) was applied to analyse their genetic relationship. Strains of high genetic homology were grouped into the same RAPD cluster (RAPD type). Sampling included, when colisepticemic or articular lesions were observed, viscera and joints from day one until 14 weeks. In the first cycle, APEC O78 was the most prevalent serotype with all isolates sharing the same resistotype and pathotype. Seven of them were included in the same RAPD cluster indicating high genetic similarity. In this cycle, APEC O111 was detected and this represents, to our knowledge, In the second cycle, APEC O2 isolates predominated at the beginning, while O78 strains appeared later until the end of the survey. APEC O2 were classified in two resistotypes, same pathotype and RAPD type. APEC 078 belonged to three resistotypes, same pathotype and three RAPD types. APEC O78 strains, differently from serotype O2, were detected from both colisepticemic viscera (such as brain, pericardium, lungs) and joints. The articular tropism of this serotype is unique as it was observed only in APEC O78 strains of this cycle and of the previous one. Moreover, RAPD molecular studies identified a specific articular O78 cluster, including two strains, which was different from other RAPD clusters including O78 and O2 colisepticemic strains

Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset

Molecular characterization of an Avian Metapneumovirus strain isolated in guinea fowls (Numida meleagridis) experiencing respiratory disease.

Avian Metapneumovirus (AMPV) subtype A and B affect mainly turkeys and chickens. However, also pheasants and guinea fowls are susceptible to natural and experimental infection. In this report an outbreak of respiratory disease, which occurred in February 2012 in a flock of guinea fowls located in an highly populated poultry area of Northern Italy, is described. An AMPV of subtype B, named aMPV/B/IT/GuineaFowl/1818/12, was isolated from oro-pharingeal swabs in chicken embryo tracheal organ cultures, and typed by a subtype specific qRT-PCR (Cecchinato et al., 2012). In order to characterize the strain, the F and G genes were sequenced using the protocol described by Cecchinato et al. (2010). Nucleotide sequences were edited and assembled using Bioedit software then aligned against analogous gene sequences of AMPV subtype B isolated in Italy or deposited/published on Genbank using Clustal W. Phylogenetic analysis was carried out under distance criterion, with neighbourjoining as algorithm, using MEGA4 software. Bootstrap values were obtained with 1.000 replicates. Branches with bootstrapping values >70 were considered significant. The trees constructed on alignments of sequence data sets of F and G genes showed that the isolate clustered with other AMPVs of subtype B isolated in Italy from turkeys and chickens after 2000. These findings do not support genetic differences correlated to the host tropism and suggest that circulation of closely related AMPV strains occurs among different avian species in densely poultry populated areas. Managerial and environmental factors involved in determining the disease outbreak are discussed

Caratterizzazione molecolare di Metapneumovirus aviare (AMPV) isolato in corso di forma respiratoria nella faraona

An outbreak of Avian metapneumovirus (AMPV) infection in Guinea fowl is reported in Northern Italy. A subtype B AMPV strain, named aMPV/B/IT/GuineaFowl/1818/12, was isolated and sequenced in F and G genes. Philogenetic analysis showed that the isolate clustered together with other AMPVs of subtype B isolated in Italy from 2001. The factors involved in determining the outbreak are discussed

Stronger and durable SARS-CoV-2 immune response to mRNA vaccines in 5–11 years old children with prior COVID-19

background and objectives: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. this study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. Methods: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the university pediatric hospital of padua and bambino-gesù hospital in rome (Italy) from december-2021 to february-2023. blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through plaque reduction neutralization test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. results: sixty children (26 [43 %] female, median age = 8 years [IQR = 7-10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS-CoV-2-naïve participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2-recovered participants recorded higher anti-S-RBD IgG and Wild-type and omicron BA.2 NAbs titers than SARS-CoV-2-naïve participants at both 1- and 6-months after vaccination. antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. both SARS-CoV-2-recovered and SARS-CoV-2-naïve participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. while children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of tregs and bregs. conclusions: mRNA vaccination triggered a higher production of specific anti-SARS-CoV-2 antibodies along with increased levels of regulatory cells in children with previous SARS-CoV-2 infection up to the following 6 months. these findings provide insights into boosting pre-existing immunity

Age level vs grade level for the diagnosis of ADHD and neurodevelopmental disorders

A number of worldwide studies have demonstrated that children born later in the school year are more likely to receive an ADHD diagnosis than their same school-year peers. There is, however, variation in findings between countries. We aimed to confirm whether relative age is associated with ADHD diagnosis, with or without comorbidities, and to investigate whether relative age is associated with ADHD type and severity, and if this age relationship is in common with other neurodevelopmental disorder. We used the Lombardy Region\u2019s ADHD registry. Data on children aged 6\ua0years and older from September 1, 2011 to December 31, 2017 were considered. We calculated incidence ratios to assess the inter-relations between relative age within the school year, using age at diagnosis of ADHD or of other psychiatric disorder, year of diagnosis, and total number of children born in Lombardy during the corresponding timeframe. Data on ADHD type, severity of diagnosed disorder clinical global impressions\u2013severity scale, and repetition of a school-grade were also considered. 4081 children, 2856 of whom with ADHD, were identified. We confirmed that the cumulative incidence of ADHD diagnosis was greatest for younger children, in particular for boys, for whom the prevalence is greater. The relative age effect was not accounted for by ADHD comorbid disorders, ADHD of combined type or severity. The relative age effect was also observed for children with other neurodevelopmental disorders (without ADHD), with a similar profile as ADHD children: the incidence ratio was 1.78 (95% CI 1.07\u20132.97; p < 0.0247) for boys diagnosed before age ten. The findings have a potential implication for diagnostic and therapeutic practice, educational advice, and policies, besides to better plan and organize service systems and appropriately inform parents, children, and citizens

Clinical characteristics, management and in-hospital mortality of patients with COVID-19 In Genoa, Italy

To describe clinical characteristics, management and outcome of COVID-19 patients; and to evaluate risk factors for all-cause in-hospital mortality