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Abstract Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)‐based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti‐spike immunoglobulin G (IgG). In this prospective cohort study, SARS‐CoV‐2 anti‐spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21–90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26‐rAd5 (Sputnik V), inactivated BBIBP‐CorV (Sinopharm), or the heterologous combination rAd26/mRNA‐1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti‐spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA‐1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03–0.3; p

Abstract Background Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2–5% of the infected individuals. Host genetic background might play a role in disease progression. Several previous studies across many countries report HLA haplotype to be one such factor. Here, we sequenced HLA-A, -B and -C of 66 individuals by Sequence-Based Typing (SBT), and compared the frequency of different alleles among ATLL patients, HAM/TSP patients, asymptomatic carriers and non-infected individuals living in Argentina. Results The frequency of HLA-A, -B and -C alleles largely matched that of the general population in Argentina. We identified HLA-A*02, HLA-B*35 and HLA-C*07 as associated to protection from ATLL (p = 0.031), susceptibility to HAM/TSP (p

Human T-lymphotropic virus type 1 (HTLV-1) is a neglected retrovirus distributed worldwide and the ethiological agent of several pathologies, such as adult T-cell leukemia/lymphoma (ATLL), a chronic myelopathy known as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). HTLV-1 presents tropism for CD4+ T cells and induces deregulation of the cytokine profile. IDH is a severe, chronic superinfected eczema generally associated with Staphylococcus aureus and/or Streptococcus beta haemolyticus infection that responds partially to antibiotic therapy but prompt recurrence develops upon treatment withdrawal. IDH could be a risk factor for progression toward both HAM/TSP and ATLL and, similarly to other diseases associated with HTLV-1, it is sub-diagnosed particularly in non-endemic areas. Here, we present a case of IDH in a young boy living in Buenos Aires with symptoms since 2010, at the age of 5. HTLV-1 infection was suspected and confirmed in 2016. The patient exhibited chronic dermatosis with exudative eruption involving mainly the scalp, retroauricular regions, neck and abdomen. Clinical evaluations, routine laboratory tests, full blood count, and HTLV-1 diagnosis for this case are included.

In this study, we evaluate the role of the MIF/CD74 axis in the functionality of CD4+ T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) HIV strain. At day 11 post-MDM infection, allogeneic co-cultures with uninfected CD4TLs plus MIF stimulus were performed. Cytokine production was evaluated by ELISA. MIF plasma levels of people with HIV (PWH) were evaluated by ELISA. The phenotype and infection rate of CD4TLs from PWH were analyzed after MIF stimulus. Intracellular cytokines and transcription factors were evaluated by flow cytometry. Data were analyzed by parametric or non-parametric methods. The MIF stimulation of HIV-infected MDMs induced an increased expression of IL-6, IL-1β and IL-8. In CD4TL/MDM co-cultures, the MIF treatment increased IL-17A/RORγt-expressing CD4TLs. Higher concentrations of IL-17A in supernatants were also observed. These results were recapitulated using transmitted/founder (T/F) HIV-1 strains. The MIF treatment appeared to affect memory CD4TLs more than naïve CD4TLs. MIF blocking showed a negative impact on IL17A+CD4TL proportions. Higher MIF concentrations in PWH-derived plasma were correlated with higher IL-17A+CD4TL percentages. Finally, MIF stimulation in PWH-derived PBMCs led to an increase in Th17-like population. MIF may contribute to viral pathogenesis by generating a microenvironment enriched in activating mediators and Th17-like CD4TLs, which are known to be highly susceptible to HIV-1 infection and relevant to viral persistence. These observations establish a basis for considering MIF as a possible therapeutic target.

Viruses play an important role in the development of certain human cancers. They are estimated to contribute 16% to all human cancers. Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy with poor prognosis. HTLV-1 viral proteins interact with mechanisms and proteins present in host cells for their own benefit, evading the immune system and promoting the establishment of disease. Several viruses manipulate the autophagy pathway to achieve their infective goals, and HTLV-1 is not the exception. HTLV-1 Tax viral protein engages NF-κB and autophagy pathways prone favoring viral replication and T cell transformation. In this review we focus on describing the relationship of HTLV-1 with the autophagy machinery and its implication in the development of ATLL.

RESUMEN Objetivo: Describir la epidemiología de la injuria renal aguda, la relación con la enfermedad renal crónica y los factores asociados a su incidencia. Métodos: Estudio de cohorte y seguimiento en una unidad de terapia intensiva de Montevideo - Uruguay. Se incluyeron pacientes ingresados entre noviembre 2014 a octubre 2015, mayores de 15 años con dos mediciones de creatinina sérica. Se excluyeron pacientes con menos de 48 horas de internación o fallecidos en ese tiempo y portadores de enfermedad renal crónica en hemodiálisis o diálisis peritoneal. No hubo intervenciones. La injuria renal aguda se definió según criterios Acute Kidney Injury Disease Improving Global Outcomes y la enfermedad renal crónica según Cronic Kidney Disease Work Group. Resultados: Se incluyeron 401 pacientes, sexo masculino 56,6%, mediana de edad 68 (rango intercuartílico - RIC 51 - 79) años. El diagnóstico al ingreso fue sepsis grave 36,3%, neurocrítico 16,3%, politrauma 15,2% y otros 32,2%. La incidencia de injuria renal aguda fue de 50,1%. El 14,1% eran portadores de enfermedad renal crónica. La incidencia de injuria renal aguda séptica fue de 75,3%. La mortalidad en los pacientes con o sin injuria renal aguda fue de 41,8 y 14% respectivamente (p < 0,001). En el análisis multivariado las variables de mayor significación para la injuria renal aguda fueron enfermedad renal crónica (odds ratio - OR 5,39 IC95% 2,04 - 14,29 p = 0,001), shock (OR 3,94 IC95% 1,72 - 9,07 p = 0,001) y sepsis grave (OR 7,79 IC 95% 2,02 - 29,97 p = 0,003). Conclusión: La incidencia de injuria renal aguda es elevada principalmente en pacientes sépticos. La enfermedad renal crónica se asoció de forma independiente al desarrollo de injuria renal aguda.

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Background: HTLV-1/2 exhibit a widespread distribution globally and are associated with severe clinical manifestations, necessitating precise viral identification for diagnosis. Currently, there are no official diagnostic guidelines, and a variety of published protocols exists. We introduce an enhanced nested real-time PCR technique followed by high-resolution melting (rtPCR-HRM), designed to offer a cost-effective and straightforward tool for the simultaneous identification of both viruses., Methods: The technique was tested in a retrospective, blinded study, involving a total panel of 110 samples, of which 47 were positive for HTLV-1, 12 for HTLV-2, and 51 tested negatives. Additionally, we compared the performance of this technique with a line immunoassay (LIA)., Results: The results demonstrate 100 % sensitivity, specificity, and diagnostic accuracy for both viruses. Sensitivity analysis indicated that at least 1 viral copy of HTLV-1 and 14.4 viral copies of HTLV-2 could be reliably detected., Conclusions: Our results indicate that rtPCR-HRM is effective in confirming HTLV-1 and HTLV-2 infection, important in Latin American countries where both viruses circulate. Furthermore, the proposed strategy provides a new tool that can be used to resolve indeterminate cases identified by Western blot, with the added advantage of being faster and simpler than n-PCR and more cost-effective than other probe-based RT-PCRs., Competing Interests: Declaration of competing interest No conflict of interest declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Solid organ transplant recipients (SOTR) commonly develop an unsatisfactory humoral response to vaccines compared to immunocompetent individuals (IC). We have previously evaluated the humoral response in liver transplant recipients (LTR) who received two-dose vaccines against SARS-CoV-2 and reported that 38 % of LTR did not produce anti-Spike antibodies. Thus, we set out to evaluate the humoral response after the third dose of SARS-CoV-2 vaccines. For this purpose, samples from a cohort of 81 LTR and 27 IC were extracted between 21 and 90 days after the third dose. Serology for anti-Spike IgG antibodies and neutralizing antibodies against Wuhan, Delta and Omicron variants were evaluated. We found that 73.5 % of LTR were responders for anti-Spike IgG, while all the IC mounted a measurable response. LTR who responded to the third dose showed significantly lower anti-Spike IgG levels and neutralizing antibodies than IC. We found that there is less neutralization in LTR compared to IC across all variants. Specifically, the neutralization titers in both groups decrease when encountering the Delta variant, and this decline is even more pronounced with the Omicron variant, compared to the Wuhan variant. Furthermore, we identified that the use of high doses of mycophenolate and advanced age were factors that negatively affected the development of anti-Spike IgG antibodies. Regarding vaccine regimes, the regime viral vector/mRNA/mRNA elicited significantly higher responses in LTR compared to other vaccine schemes. In addition to the recommended and necessary booster doses in this population, strategies that achieve adequate immunization should be evaluated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this study, we evaluate the role of the MIF/CD74 axis in the functionality of CD4 + T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) HIV strain. At day 11 post-MDM infection, allogeneic co-cultures with uninfected CD4TLs plus MIF stimulus were performed. Cytokine production was evaluated by ELISA. MIF plasma levels of people with HIV (PWH) were evaluated by ELISA. The phenotype and infection rate of CD4TLs from PWH were analyzed after MIF stimulus. Intracellular cytokines and transcription factors were evaluated by flow cytometry. Data were analyzed by parametric or non-parametric methods. The MIF stimulation of HIV-infected MDMs induced an increased expression of IL-6, IL-1β and IL-8. In CD4TL/MDM co-cultures, the MIF treatment increased IL-17A/RORγt-expressing CD4TLs. Higher concentrations of IL-17A in supernatants were also observed. These results were recapitulated using transmitted/founder (T/F) HIV-1 strains. The MIF treatment appeared to affect memory CD4TLs more than naïve CD4TLs. MIF blocking showed a negative impact on IL17A + CD4TL proportions. Higher MIF concentrations in PWH-derived plasma were correlated with higher IL-17A + CD4TL percentages. Finally, MIF stimulation in PWH-derived PBMCs led to an increase in Th17-like population. MIF may contribute to viral pathogenesis by generating a microenvironment enriched in activating mediators and Th17-like CD4TLs, which are known to be highly susceptible to HIV-1 infection and relevant to viral persistence. These observations establish a basis for considering MIF as a possible therapeutic target.

Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti-spike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21-90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03-0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2-0.7; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA-1273 (OR, 13.1; 95% CI, 2.3-72.9; p = 0.003). In LTRs anti-spike IgG concentrations showed a very good correlation with NA titers (R 2 = 0.949; 95% CI, 0.919-0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA-1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Viruses play an important role in the development of certain human cancers. They are estimated to contribute 16% to all human cancers. Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy with poor prognosis. HTLV-1 viral proteins interact with mechanisms and proteins present in host cells for their own benefit, evading the immune system and promoting the establishment of disease. Several viruses manipulate the autophagy pathway to achieve their infective goals, and HTLV-1 is not the exception. HTLV-1 Tax viral protein engages NF-κB and autophagy pathways prone favoring viral replication and T cell transformation. In this review we focus on describing the relationship of HTLV-1 with the autophagy machinery and its implication in the development of ATLL., 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 © 2021 Ducasa, Grasso, Benencio, Papademetrio, Biglione, Kashanchi, Berini and Garcia.)

Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.