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Introduction: Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. Methods: YWVH under suppressive ART were included and compared to a group of HIV‐negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. Results: Thirty‐two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4‐ and CD8‐T cells showed high levels of activation (HLA‐DR/CD38), IL‐7 receptor expression (CD127) and exhaustion (TIM‐3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T‐cell activation (HLA‐DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD‐1) levels with the CD4/CD8 ratio among YWVH. HLA‐DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16high NK‐cell subsets, exhaustion T‐cell levels (CD57, TIM3) and NK cells activation levels. Conclusions: Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to seek correlates of immune protection in HIV infection. We sought to elucidate the association between the presence of human leucocyte antigen ( HLA) alleles, as well as killer immunoglobulin receptor ( KIR) genotypes, and the susceptibility to HIV infection in a Spanish cohort of HIV-exposed seronegative ( HESN) individuals. Methods A total of 152 individuals were evaluated: 29 HESN individuals in stable heterosexual relationships with an HIV-infected partner admitting high-risk sexual intercourse for at least 12 months prior to inclusion in the study, 61 HIV-infected patients and 62 healthy controls. HLA class I and II alleles and KIR genotypes were assessed in genomic DNA from all individuals in the study by polymerase chain reaction−sequence-specific oligonucleotide ( PCR- SSO) using bead array technology. Results HESN individuals showed a higher prevalence of HLA-A3 (62%) and HLA-B44 (83%) supertypes compared with HIV-infected individuals (42% and 66%, respectively). Regarding specific HLA alleles, HESN individuals had a higher prevalence of HLA-A*33:01, DRB1*04 and DQB1*03:02 alleles (14%, 34% and 31%, respectively) and a lower prevalence of the HLA-A*02:01 allele (27%) than HIV-infected patients (3%, 15%, 11% and 52%, respectively; P < 0.05). Interestingly, in a multivariate analysis, only the presence of DQB1*03:02 and the absence of A*02:01 alleles were independently associated with HESN status [odds ratio ( OR) 3.4 (95% confidence interval ( CI) 1.1-10.5) and 0.4 (95% CI: 0.1-0.9), respectively; P < 0.05]. No KIR genotype was associated with susceptibility to HIV infection. Conclusions Our data showed that the presence of the HLA class II allele DQB1*03:02 was a correlate of immune protection against HIV infection, while the presence of the HLA class I allele A*02:01 was associated with being infected with HIV. [ABSTRACT FROM AUTHOR]

Background: Although the effects of probiotics on the immune system have been extensively evaluated under disease states, their role in healthy situations remains unclear, since changes are hardly expected under immunological homeostasis. EFSA indicates that vaccination protocols could be used to evaluate the potential role of probiotics to improve the immune response against antigen challenges. The aim of the study was to evaluate the effect of Lactobacillus coryniformis CECT5711 (Lc) on the specific immunity of healthy volunteers undergoing vaccination with Hepatitis A virus (HAV). Methods: One hundred twenty-three healthy adults were randomised into three groups to follow a 6-week (wk) intervention and all received an intramuscular HAV vaccine 2 weeks after starting the intervention: 1) PRO1 received Lc for 2weeks (1 capsule/day; 3 x 109 CFU/capsule) and placebo capsules after vaccination; 2) PRO2 received a daily capsule of Lc (3 x 109 cfu/day) before and after the challenge; 3) Control group (C) received a daily placebo capsule before and after the vaccine. Blood samples were collected at the beginning (visit 1; V1) and after 2 (V2) and 6 weeks (V3) of the intervention. At each visit, lymphocyte subset counts and cytokine levels were analysed. Specific HAV antibodies were analysed at V1 and V3. To evaluate differences between groups, one-way ANOVA with Bonferroni post-hoc test were used regarding lymphocyte subset counts and specific HAV antibodies production, and Friedman test of related samples and Kendall concordance coefficient for cytokines production. Chi square test was used to analyse seroconversion rates. Results: Specific HAV antibodies were significantly higher in PRO1 (50.54 ± 29.57) compared to C (36.23 ± 16. 45) (P = 0.017) and showed an intermediate value in PRO2 (41.61 ± 15.74). Seroconversion rates were similar in the three groups (97.3, 92.3 and 97.4% in C, PRO1 and PRO2 respectively). Memory T-helper lymphocytes increased in V3 vs. V1 (P = 0.032) in PRO2. No differences were found in cytokine concentrations. Conclusion: Mixed results have been found regarding the usefulness of Lc supplementation to increase the antigen-specific antibody response to an immune challenge. Clinical trial registration number: EudraCT Number 2016-000183-42. Registered 19 January 2016. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Simple Summary: T-LGLL and CLPD-NK are two indolent lymphoproliferative syndromes whose main symptoms derive from the cytopenia(s). A proportion of patients harbor STAT3 mutations that appear to play an important role in the pathogenesis of the disease. The aim of our retrospective study was to describe the main clinicobiological characteristics, response to therapy and outcome in a large cohort of T-LGLL and CLPD-NK patients diagnosed at a single institution. The impact of STAT3 mutations on the behaviour of the disease and the survival of these patients compared to the age- and sex-matched general population are also evaluated. For the first time, we show that the survival of patients with these two diseases does not differ from that of a matched general Spanish population, confirming the indolent course of these entities. T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorder of natural killer (NK) cells are two infrequent diseases characterized by clonal expansions of cytotoxic T lymphocytes and NK cells, respectively. Somatic mutations of STAT3 are involved in the pathogenesis of these entities. We describe the clinicobiological features, mutational status of STAT3/STAT5B, treatment and outcome of 131 patients. Neutropenia was the most frequent finding at diagnosis, followed by anemia. Concurrent hematological disorders were diagnosed in 37% of patients and autoimmune conditions and solid tumors in 17% and 15%, respectively. All patients who needed treatment belonged to the CD8+CD57+ group. Remarkably, patients included in the CD4+ group had a higher association with solid tumors (p = 0.037). STAT3 mutations were found in 17% of patients, mainly Y640F and D661Y mutations. Patients carrying STAT3 mutations more frequently presented with anemia, neutropenia, high LDH, high large granular lymphocyte counts and need for treatment (p = 0.0037). Methotrexate was the most frequently used agent (72% of cases). The overall response rate to all treatments was 50%. The 10-year overall survival of this series was 78%, with no differences according to the mutational status of STAT3. We compared the survival of these patients with the general Spanish population and no differences were found, confirming the indolent nature of these hematological malignancies. Our study further extends findings documented by others on the clinical behavior of the disease and the impact of STAT3, and for the first time analyzes survival compared to a matched general Spanish population. [ABSTRACT FROM AUTHOR]