Departamento de Salud

Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/ CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery

2025-09-08T00:00:00Z

Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/ CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery Garrido-Rodríguez, Vanesa; Bulnes-Ramos, Ángel; Olivas-Martínez, Israel; Pozo-Balado, María del Mar; Tejerina-Picado, Francisco; Gutiérrez, Félix; Marco-Sánchez, Cristina; Tiraboschi, Juan Manuel; Castillo-Navarro, Antonia; Bernal, Enrique; García-Guerrero, María C; Puertas, María C; Peraire, Joaquim; Rull, Anna; Martínez-Picado, Javier; Pacheco, Yolanda María Background: People living with chronic HIV (PLWH) show immune dysfunction, despite viral suppression and normal CD4 recovery, particularly those with low CD4/CD8 ratios. Subjacent cellular alterations of such a reliable marker of clinical progression remain elusive. Methods: Categorization by CD4/CD8 ratio after three year of therapy (R < 0.8/R > 1.2, n = 28/n = 24) and post-hoc reclassification by nadir-CD4 (N ≤ 350/N > 350) were performed in PLWH achieving viral suppression and CD4 ≥ 500. CD4 T cell-associated viral reservoir, as well as metabolism-related gene expression, glucose uptake ability, relative telomere length (RTL), and thymic output for CD4 and CD8 T cells, were determined. Results: Patients with a CD4/CD8 ratio < 0.8 exhibited reduced CD8 T-cell glucose uptake ability after stimulation (p = 0.007) and trends to shorter RTL (p = 0.093) and to larger CD4-associated viral reservoir (p = 0.068) than R > 1.2. Differently, patients with nadir ≤350 exhibited altered CD4 and CD8 T-cell expression of metabolism-related genes, although no differences in glucose uptake ability, and shorter RTL in both cell subsets, but similar viral reservoir to patients with nadir >350. Remarkably, viral reservoir and both CD4 and CD8 thymic output showed inverse associations (r = -0.623, p = 0.01 and r = -0.661, p = 0.038, respectively). Conclusion: A low CD4/CD8 ratio in chronic PLWH stands on a larger viral reservoir in CD4 T cells and metabolic alterations in CD8 T cells, probably related to its exhaustion and compromised effector functionality, and thymic output could contribute to such alterations. Patients with lower nadir-CD4 showed a resting-like CD4 phenotype and a metabolically active CD8 subset, without further viral reservoir extension. Persistence of low CD4/CD8 ratio and low nadir-CD4 counts seems to rely on different immune damage.

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients

2020-10-06T00:00:00Z

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients Cordero, Elisa; Bulnes-Ramos, Ángel; Aguilar-Guisado, Manuela; González-Escribano, Francisca; Olivas, Israel; Torre-Cisneros, Julián; Gavaldá, Joan; Aydillo, Teresa; Moreno, Asunción; Montejo, Miguel; Fariñas, María Carmen; Carratalá, Jordi; Muñoz, Patricia; Blanes, Marino; Fortún, Jesús; Suárez-Benjumea, Alejandro; López-Medrano, Francisco; Roca, Cristina; Lara, Rosario; Pérez-Romero, Pilar Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.

Evaluation of a non-invasive screening approach to determine hepatitis E virus status of pig farms

2020-10-03T00:00:00Z

Evaluation of a non-invasive screening approach to determine hepatitis E virus status of pig farms Risalde, María A; Rivero-Juárez, Antonio; Frías, Mario; Olivas, Israel; López-López, Pedro; García-Bocanegra, Ignacio; Brieva, Teresa; Caballero-Gómez, Javier; Camacho, Ángela; Fernández-Molera, Vicente; Gómez-Villamandos, José Carlos; Rivero, Antonio Background Identifying pig farms infected with hepatitis E virus (HEV) is a key aspect to implement surveillance programmes for this emerging zoonotic agent. Detection of HEV in blood has several drawbacks, including animal handling, economic costs and animal stress. The objective of this study was to evaluate the effectiveness of a non-invasive screening approach for determining the HEV status of pig farms under different management systems. Methods Forty stool samples randomly collected from the pen floor of 17 intensive pig farms and the yard of nine extensive ones were tested for HEV RNA. The invasive method used to confirm the HEV status of the farm was HEV RNA analysis of serum samples randomly collected from 40 animals on each farm. Results Twenty-one HEV-positive farms were detected by invasive and non-invasive methods. No positive serum or stool samples were detected on five intensive farms. A high intertest agreement (K=1; P<0.00001) was observed between both methodologies, showing the stool screening approach a 100 per cent of sensitivity and specificity with respect to the invasive method. Likewise, a significant negative relationship was observed between the HEV within-farm prevalence and the number of the first HEV-positive stool sample found (Spearman’s rho=−0.64; P=0.0004). This negative relationship was higher in intensively managed farms. Conclusion This non-invasive screening approach could be reliably applied in a large-scale surveillance programme for determining the HEV status of pig farms under different management systems.

Lower frequency of anti-citrullinated protein antibodies among early arthritis patients with high body mass index

2020-12-03T00:00:00Z

Lower frequency of anti-citrullinated protein antibodies among early arthritis patients with high body mass index Moreno-Fresneda, Pablo; Triguero-Martínez, Ana; Olivas-Martínez, Israel; Ortiz-Aljaro, Pilar; González-Escribano, María Francisca; Nuño-Nuño, Laura; Ortiz, Ana M; González-Álvaro, Isidoro OBJECTIVES: To investigate the role of body mass index (BMI) in the phenotypic and genotypic characteristics of early arthritis patients. METHODS: We analysed the clinical and laboratory parameters from the baseline visit of patients (670 patients [78.51% women]) included in the PEARL study. The WHO definition for low weight, normal weight, overweight and obesity (BMI <18.5, 18.5–25, 25–30 or ≥30 kg/m2, respectively) was applied. Anticitrullinated protein antibodies (ACPA) were studied by ELISA and HLA-DRB1* were genotyped by sequence speci c oligonucleotide probes. The relationship between BMI classification and other variables was analysed using Kruskall-Wallis, Anova and Chi-Square tests. Then multivariate logistic regression was performed to establish the role of BMI in ACPA positivity and ordered logistic regression to establish its relationship with ACPA level. RESULTS: Among the patients studied, 255 (38.06%) were considered overweight and 136 (20.3%) obese. High BMI patients had significantly more pain perception and disability than normal weight patients, whereas no clear differences in disease activity were observed between high BMI and normal weight patients. ACPA positivity was significantly less frequent in overweight and obese patients compared to normal BMI patients. This information was confirmed by adjusting for smoking habit and the presence of shared epitope. CONCLUSIONS: Our data support the theory that high BMI patients suffer more frequently from ACPA-negative RA. Nevertheless, although no disease activity differences were observed, these patients showed higher pain and disability scores since the beginning of disease.