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In this paper we present a remote sensing technique, based on very high spatial resolution Quickbird satellite data, aimed to map burnt forested areas located in alpine environment hit by winter fires occurred in Lombardia Region in the 2005 year. Quickbird satellite images have a spatial resolution of 2.5 m and are characterized by 4 spectral bands covering the regions of blue, green, red and near infrared. Burnt areas were automatically extracted by using an object oriented classification combined with a connectivity algorithm developed with the aim to join burnt isolates pixel with the main body of the area hit by fire. The proposed algorithm is based on the exploitation of a Gaussian function that produces a degree of membership to be burnt for every pixel not classified as burnt by means of the preliminary automatic classification. The membership function is established on the base of the spatial distance and it decrease according the full width at half maximum of the Gaussian function. The produced maps have been compared with the burnt area boundaries obtained by means of field survey based on GPS measurements; this allowed us to estimate the goodness of the proposed method. The comparison between the results produced by the connectivity algorithm and the reference measured in ground showed high degrees of accuracy with errors ranging from 3 to 20%.

CD4 T cells play a key role in Epstein Barr virus (EBV) infection, by modulating latent antigen expression, and exhibiting cytotoxic and regulatory properties. Our aim was to evaluate the presence of Granzyme B (GZMB) and Foxp3 CD4 T cells at different EBV infection status and latency profiles. We examined CD4, GZMB, Foxp3, IL10, TGF-β, CD4-GZMB and CD4-Foxp3 expression at the tonsils of pediatric patients with different infective status and EBV latency profiles. CD4+, GZMB+, Foxp3+, CD4-GZMB+ and CD4-Foxp3+ cell counts were higher at the interfollicular region. Higher expression of CD4-GZMB was found in primary infected patients compared to healthy carriers. In patients that expressed latency III antigens, we demonstrated lower CD4+, CD4-GZMB+, CD4-Foxp3+ expression; a negative correlation between the immunoregulatory cytokine IL-10+ and GZMB+ as well as a positive correlation of IL-10+ and CD4+. In patients expressing the lytic protein BMRF1, a positive correlation of TGF-β+ with CD4-GZMB+ and CD4-Foxp3+ was observed. Our findings indicate that CD4-GZMB+ cells are involved in the restriction of primary EBV infection in pediatric patients, which could partially explain the lack of symptoms, whereas both CD4-GZMB+ and CD4-Foxp3+ cells could be involved in the modulation of latency., (© 2024. The Author(s).)

Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus-host interaction. KEY MESSAGES: HCV and HCV/HIV displayed similar plasma-EV size and concentration. EVs- derived miRNA profile was characterized by NGS. 37 SDE miRNAs between HCV and HCV/HIV were observed. SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer., (© 2023. The Author(s).)

Macrophages are exceptionally flexible cells. The presence of inflammatory cytokines such as IFN-γ and TNF-α results in an M1 (CD68) activation, while cytokines such as IL-10 or TGF-β induce the M2 (CD163) activation. Our aim was to study the behavior of peripheral cytokines involved in macrophage polarization and relate them with tissue findings to further comprehend the role of macrophages in EBV pediatric infection. We studied cytokine expression in tonsils and peripheral blood samples of children in different stages of infection. Peripheral cytokines were compared with macrophage polarization markers and viral protein expression in tonsils. Only IL-10 showed a negative correlation between compartments, exclusively in patients undergoing viral reactivation (R). Higher expressions of peripheral IL-1β, IL-23, and IL-12p40 in R children were observed. Lower expressions of local and peripheral TNF-α in patients with broader expressions of latent and lytic viral proteins were demonstrated. In healthy carrier (HC) patients, IL-23 positively correlated with CD163, and IP-10 positively correlated with CD68. Our results indicated that EBV might modulate antigen expression in the presence of TNF-α and influence peripheral cytokine expression differently in each stage of infection. Moreover, peripheral cytokines might have a particular role in macrophage polarization in HC.

In 2017, the World Health Organization (WHO) confirmed a new entity, Epstein Barr virus (EBV) + Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS). Traces of EBV transcripts were described in lymphomas, including DLBCL, that were diagnosed as EBV negative by conventional methods. The aim of this study was to detect viral genome by qPCR, as well as LMP1 and EBNA2 transcripts, with a more sensitive method in DLBCL cases from Argentina. Fourteen cases originally considered as EBV negative expressed LMP1 and/or EBNA2 transcripts. In addition, LMP1 and/or EBNA2 transcripts were also observed in bystander cells. However, EBERs+ cells cases by conventional ISH showed higher numbers of cells with LMP1 transcripts and LMP1 protein. In the cases that were EBERS- in tumor cells but with expression of LMP1 and/or EBNA2 transcripts, the viral load was below the limit of detection. This study provides further evidence that EBV could be detected in tumor cells by more sensitive methods. However, higher expression of the most important oncogenic protein, LMP1, as well as increased viral load, are only observed in cases with EBERs+ cells by conventional ISH, suggesting that traces of EBV might not display a key role in DLBCL pathogenesis., (© 2023 UICC.)

Background: Angiotensin-converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19. Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2). Transcriptomic studies showed that children display lower ACE2 than adults, though gene expression levels do not always correlate with protein levels. We investigated the effect of age on ACE2 and TMPRSS2 protein expression in alveolar type II (AT2) cells in the lungs of children compared to adults. We also analysed the ratio of Ang-(1-7) to Ang II as a surrogate marker of ACE2 activity in the subjects' lung parenchyma., Methods: Ang II and Ang-(1-7) levels and ACE2 and TMPRSS2 protein expression were measured by radioimmunoassay and immunohistochemistry, respectively., Results: The amount of ACE2-expressing AT2 cells and ACE2 protein content were lower in children than in adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells. Children presented lower Ang-(1-7)/Ang II ratio than adult suggesting lower ACE2 activity in children. TMPRSS2 protein expression was not influenced by age., Conclusions: These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection., Category of Study: Clinical original research IMPACT: Children display lower ACE2 protein content and activity compared to adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells TMPRSS2 protein expression was not influenced by age. These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Epstein-Barr Virus (EBV) is a tumor associated virus that modulates not only the infected cells but also innate and adaptive immunity. Macrophages play a key role in tumor development and progression. Particularly, the M2 phenotype (CD163) with anti-inflammatory activity contributes to a favorable microenvironment for tumor development while the M1 (CD68) proinflammatory phenotype contributes to a restrictive one. In the context of pediatric EBV infection, little is known about macrophage contribution to PD-L1 expression, a molecule involved in immune exhaustion. We studied tonsils of primary infected (PI), healthy carriers (HC), reactivated (R), and not infected (NI) pediatric patients. Positive correlations were demonstrated for CD68+PD-L1+ in R and for CD163+PD-L1+ only in PI. Furthermore, CD163+PD-L1+ cell numbers were higher than PD-L1+CD68+ in PI patients. In addition, a positive correlation between PD-L1+CD163+ cells and LMP1 viral latent protein was observed in PI patients, and a positive correlation between PD-L1+CD68+ cells and BMRF1 lytic antigen was demonstrated. A positive correlation between TGF-β and PD-L1 expression was demonstrated in HC patients. Our findings indicate that EBV's lytic and latent antigens might be regulating macrophages' PD-L1 expression, particularly in PI patients, whereas, surprisingly, only TGF-β could be related to total PD-L1 upregulation. Given the relevance of macrophages and the PD-1/PD-L1 pathway in tumor progression and survival, more studies in early EBV infection could help to develop EBV-associated tumor therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moyano, Ferressini, De Matteo, Preciado and Chabay.)

In pediatric Hodgkin lymphoma (HL), the inability of the cytotoxic microenvironment induced by EBV presence to eliminate tumor cells could reflect the fact that the virus might be able to induce the expression of exhaustion markers to evade an immune response. Therefore, the expression of exhaustion markers in pediatric EBV-associated HL was evaluated. A balance between cytotoxic GrB and Th1 Tbet markers with regulatory Foxp3 was proved in EBV+ cases. In addition, exclusively in EBV-associated cHL, a correlation between PD-1 and LAG-3 expression was observed. Furthermore, those cases also displayed a trend to worse survival when they expressed LAG-3 and inferior event-free survival when both PD-1 and LAG-3 molecules were present. Therefore, even though a cytotoxic and inflammatory environment was supposed to be triggered by EBV presence in pediatric cHL, it seems that the virus may also induce the synergic effect of inhibitory molecules LAG-3 and PD-1 in this series. These observations may reflect the fact that the permissive and exhausted immune microenvironment succeeds to induce lymphomagenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jimenez, Mangiaterra, Colli, García Lombardi, Preciado, De Matteo and Chabay.)

Macrophage activation plays a key role in liver disease progression. Soluble CD163 (sCD163) is a specific macrophage activation biomarker useful for clinical estimating damage severity and predicting outcome in different liver conditions. sCD163 performance as a non-invasive marker of liver damage was evaluated in plasma samples at time of biopsy in 120 patients with different hepatic conditions (56 HCV, 20 HCV/HIV, 10 HBV and 34 MAFLD). sCD163 values were compared with those of healthy donors and analyzed related to histological damage. sCD163 together with other clinical parameters were used to create a logistical regression model to predict significant fibrosis. Only patients with viral hepatitis showed higher sCD163 values compared to the control group (HCV p<0.0001; HCV/HIV p<0.0001; HBV p = 0.0003), but no significant differences regarding fibrosis stages were observed. The proposed model predicts fibrosis severity using the logarithm sCD163 concentration, platelet count and age, it demonstrated to be a good marker for the HCV monoinfected group (AUROC 0.834) and an excellent one for the HCV/HIV co-infected group (AUROC 0.997). Moreover, the model displayed a diagnostic performance similar to FIB-4 in HCV cases and FIB-4 and APRI in HCV/HIV coinfected cases, and it even managed to correctly classify some cases that had been misclassified. The proposed model is able to determine, in a non-invasive way, the liver fibrosis stage of HCV and HCV/HIV patients, so after validation, it could be used in a complementary way in the clinical practice whenever APRI and FIB-4 failed to determine damage severity in HCV and HCV/HIV cases., Competing Interests: The authors disclose no conflicts of interest.

Segmental dilatation of the intestine is an extremely rare congenital entity characterized by a local dilation of the intestine without distal obstruction or the absence of ganglion cells. We present the case of a patient in the neonatal period with typical clinical features in absence of other comorbidities, shortly published in the bibliography. We also describe the surgical resolution and the pathological results., Competing Interests: None, (Sociedad Argentina de Pediatría.)

The immune response is critical in NAFLD pathogenesis, but the liver infiltrate's composition and the role of each T cell population is still up for debate. To characterize liver pathogenesis in pediatric and adult cases, frequency and localization of immune cell populations [Cytotoxic T Lymphocytes (CD8+), T helper Lymphocytes (CD4+), Regulatory T lymphocytes (Foxp3+) and Th17 (IL-17A+)] were evaluated. In portal/periportal (P/P) tracts, both age groups displayed a similar proportion of CD8+ and CD4+ lymphocytes. However, comparable Foxp3+ and IL-17A+ cell frequencies were observed in pediatric cases, meanwhile, in adults Foxp3+ was higher than IL-17A+ cells. Interestingly, IL-17A+ lymphocytes seemed to be nearly exclusive of P/P area in both age groups. In intralobular areas, both pediatric and adult cases showed CD8+ lymphocytes predominance with lower frequencies of CD4+ lymphocytes followed by Foxp3+ . Severe inflammation was associated with higher intralobular Foxp3+ lymphocytes (p = 0.026) in children, and lower P/P Foxp3+ and higher IL-17A+ lymphocytes in adults. All cases with fibrosis ≥ 2 displayed P/P low Foxp3+ and high IL-17A+ lymphocyte counts. Pediatric cases with worse steatosis showed high P/P CD4+ (p = 0.023) and intralobular CD8+ (p = 0.027) and CD4+ cells (p = 0.012). In NAFLD cases, the lymphocyte liver infiltrate composition differs between histological areas. Treg and Th17 balance seems to condition damage progression, denoting their important role in pathogenesis.

The Epstein-Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV) and human T-lymphotropic virus (HTLV-1) are lymphomagenic viruses with region-specific induced morbidity. The RIAL-CYTED aims to increase the knowledge of lymphoma in Latin America (LA), and, as such, we systematically analyzed the literature to better understand our risk for virus-induced lymphoma. We observed that high endemicity regions for certain lymphomas, e.g., Mexico and Peru, have a high incidence of EBV-positive lymphomas of T/NK cell origin. Peru also carries the highest frequency of EBV-positive classical Hodgkin lymphoma (HL) and EBV-positive diffuse large B cell lymphoma, not otherwise specified (NOS), than any other LA country. Adult T cell lymphoma is endemic to the North of Brazil and Chile. While only few cases of KSHV-positive lymphomas were found, in spite of the close correlation of Kaposi sarcoma and the prevalence of pathogenic types of KSHV. Both EBV-associated HL and Burkitt lymphoma mainly affect young children, unlike in developed countries, in which adolescents and young adults are the most affected, correlating with an early EBV seroconversion for LA population despite of lack of infectious mononucleosis symptoms. High endemicity of KSHV and HTLV infection was observed among Amerindian populations, with differences between Amazonian and Andean populations.

In Argentina, Epstein-Barr virus (EBV) presence is associated with Hodgkin lymphoma (HL) in patients younger than 10 years, suggesting a relationship between low age of EBV infection and HL. Given that HL is derived from germinal centers (GC), our aim was to compare EBV protein expression and microenvironment markers between pediatric HL patients and EBV+GC in children., Methods: EBV presence and immune cell markers were assessed by in situ hybridization and immunohistochemistry (IHC)., Results: Viral latency II pattern was proved in all HL patients and in 81.8% of EBV+ tonsillar GCs. LMP1 and LMP2 co-expression were proved in 45.7% HL cases, but only in 7.7% EBV+ GC in pediatric tonsils. An increase in CD4+, IL10, and CD68+ cells was observed in EBV+ GC. In pediatric HL patients, only the mean of IL10+ cells was statistically higher in EBV+ HL., Conclusions: Our findings point us out to suggest that LMP1 expression may be sufficient to drive neoplastic transformation, that an immune regulatory milieu counteracts cytotoxic environment in EBV-associated Hodgkin lymphoma, and that CD4+ and CD68+ cells may be recruited to act in a local collaborative way to restrict, at least in part, viral-mediated lymphomagenesis in tonsillar GC.

Neurothekeomas, or simply nerve sheath myxomas, are rare benign skin neoplasms. They are believed to derive from peripheral nerve sheath transformation and are typically more prevalent in females. They tend to be found mainly on the upper limbs as well as head and neck locations. In this report, we detail two children with neurothekeomas, describe the fundamental clinical manifestations, and review the current literature., (© 2019 Wiley Periodicals, Inc.)

In classic Hodgkin lymphoma (cHL), Epstein Barr virus (EBV) association varies worldwide. Aims: Our aim was to analyze EBV association with pediatric cHL for the last 28 years. Methods: EBV presence was evaluated by EBERs in situ hybridization and LMP1 immunohistochemistry. Results: Until 2008, we found in pediatric cHL a similar percentage of EBV presence to those observed in adult cHL from developed populations. Nevertheless, in the last 8 years, an unexpected difference in cHL EBV association was proven, along with a slight bias of EBV association with the nodular sclerosis (NS) subtype. Concerning histological subtype distribution, even though MC still prevailed in the whole series, those cases diagnosed as NS showed a sustained rise from 1989 until today. Conclusion: Variations of EBV association of cHL related to geography, age, ethnicity, and histological type have been largely described when compared with different world regions, but interestingly, this single-center revised series brought to light the dynamic process behind the evolution of this relationship over time., (Copyright © 2019 De Matteo, García Lombardi, Preciado and Chabay.)

In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity., (© 2019 John Wiley & Sons Ltd.)

Epstein Barr virus (EBV) gains access to the host through tonsillar crypts. Our aim was to characterize microenvironment composition around EBV+ cells in tonsils from pediatric carriers, to disclose its role on viral pathogenesis. LMP1 expression, assessed by immunohistochemistry (IHC), was used to discriminate EBV + and - zones in 41 tonsil biopsies. Three regions were defined: Subepithelial (SE), interfollicular (IF) and germinal center (GC). CD8, GrB, CD68, IL10, Foxp3, PD1, CD56 and CD4 markers were evaluated by IHC; positive cells/100 total cells were counted. CD8+, GrB+, CD68+ and IL10+ cells were prevalent in EBV+ zones at the SE region (p < 0.0001, p = 0.03, p = 0.002 and p = 0.002 respectively, Wilcoxon test). CD4+ and CD68+ cell count were higher in EBV + GC (p = 0.01 and p = 0.0002 respectively, Wilcoxon test). Increment of CD8, GrB and CD68 at the SE region could indicate a specific response that may be due to local homing at viral entry, which could be counterbalanced by IL10, an immunosuppressive cytokine. Additionally, it could be hypothesized that CD4 augment at the GC may be involved in the EBV-induced B-cell growth control at this region, in which macrophages could also participate.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort., Patients and Methods: Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples., Results: HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848)., Conclusion: Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.

Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in diffuse large B cell lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina. An unexpected number of cells expressed lytic transcripts, being transcribed at the BZLF1, BHRF1, and BLLF1 locus, by real-time quantitative polymerase chain reaction. This lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, and a positive correlation between lytic and latent genes was confirmed, revealing a close link between their expressions in EBV+ DLBCL pathogenesis. Remarkably, BZLF1 displayed a negative correlation with CD4 cell counts, and this could be in part justified by the restriction of antigen presentation previously reported. The direct correlation for the late lytic gene BLLF1 and IFNγ in this series could represent a specific response directed towards this antigen. Interleukin 10 transcripts also displayed a positive correlation with lytic expression, indicating that regulatory mechanisms could be also involved on EBV-associated DLBCL pathogenesis in our series. Complete lytic reactivation in EBV-positive tumours could potentially kill EBV-positive malignant cells, providing a tool to promote tumour cell killing mediated by EBV as a complementary treatment strategy., (Copyright © 2017 John Wiley & Sons, Ltd.)

Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.

Introduction: The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties., Aims: This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model., Results: The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages., Conclusion: Our findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research.

Plasmablastic lymphoma is a rare and aggressive subtype of diffuse large B cell non-Hodgkin lymphoma, originally described in the oral cavity of male adults with acquired immune deficiency syndrome. It is composed of neoplastic ceils which resemble immunoblasts but present immunophenotype distinctive of plasma cell and Epstein-Barr virus latent infection. In children, it is an even rarer disease. We present a case of oral plasmablastic lymphoma in a vertically transmitted human immunodeficiency virus-positive five-year-old child., (Sociedad Argentina de Pediatría.)

Epstein-Barr virus (EBV) is a B lymphotropic human herpesvirus. Two models, germinal center (GC) and direct infection, describe how EBV infects B-cells. Since in Argentina primary infection is mostly subclinical at young ages, children represent an interesting population where to analyze EBV infection, especially considering that most studies are usually performed in adults. Tonsil biopsies from pediatric carriers were studied to describe infection characteristics. EBV+ lymphocytes at the interfollicular region were mainly observed. Latency III pattern in subepithelial (SubEp) lymphocytes was observed at young ages, probably indicating a recent infection. In older patients EBV was mostly detected in epithelial cells, suggesting that they could have been infected some time ago. This finding was sustained by tonsillar viral load, which was higher in cases with LMP1+SubEp cells vs. LMP1+nonSubEp cells (p = 0.0237, Mann-Whiney test). Latency III was prevalent and related to the GC, while latency II was associated with non-GC (p = 0.0159, χ2 test). EBERs+/IgD+ cells were statistically prevalent over EBERs+/CD27+ cells (p = 0.0021, χ2 test). These findings indicated that both EBV infection models are not mutually exclusive and provide some basis for further understanding of EBV infection dynamics. Moreover, we provide a more accurate explanation of EBV infection in pediatric asymptomatic carriers from a developing country.