Deep immune cell phenotyping and induced immune cell responses at admission stratified by BMI in patients hospitalized with COVID-19: An observational multicenter cohort pilot study.

Introduction: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients.

Methods And Results: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese).

Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections.

Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19.

Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials.

Purpose: Patients with chronic lymphocytic leukemia (CLL) have increased risk of severe infections. Although adaptive immune dysfunction is well described, clinical tools for identifying patients at risk are lacking, warranting investigation of additional immune components. In contrast to chemotherapy, targeted agents could spare or even improve innate immune function.

Added Value of Reanalysis of Whole Exome- and Whole Genome Sequencing Data From Patients Suspected of Primary Immune Deficiency Using an Extended Gene Panel and Structural Variation Calling.

Background: Knowledge of the genetic variation underlying Primary Immune Deficiency (PID) is increasing. Reanalysis of genome-wide sequencing data from undiagnosed patients with suspected PID may improve the diagnostic rate.

Methods: We included patients monitored at the Department of Infectious Diseases or the Child and Adolescent Department, Rigshospitalet, Denmark, for a suspected PID, who had been analysed previously using a targeted PID gene panel (457 PID-related genes) on whole exome- (WES) or whole genome sequencing (WGS) data.

Impact of Age and HIV Status on Immune Activation, Senescence and Apoptosis.

Introduction: Residual immune dysfunctions, resembling those that occur during normal aging, may persist even in well-treated people with HIV (PWH), and accelerated aging has been proposed. We aimed to determine if HIV infection is an independent risk factor for T-cell immune dysfunctions including increased immune activation, senescence and apoptosis. Moreover, in PWH we aimed to identify the associations between age and immune activation, senescence and apoptosis.

Increased systemic inflammation and altered distribution of T-cell subsets in postmenopausal women.

Aim: To investigate markers of systemic inflammation in pre- and postmenopausal women and identify possible predictors of systemic inflammation with menopause.

Methods: Cross-sectional study of 69 healthy women between 45- and 60 years. Blood samples were collected to assess leukocyte subsets and plasma cytokines.

Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection.

Background: In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion.

Increased proportions of B cells with spontaneous production of interleukin-10 in HIV-infected individuals are normalized during combination antiretroviral therapy: a longitudinal study.

Interleukin-10 (IL-10)-producing B cells (B10 cells) may inhibit HIV-specific T cells and are elevated in untreated HIV infection. We aimed to determine the effect of combination antiretroviral treatment (cART) on the proportion of B10 cells. Furthermore, we compared B10-cell proportions in HIV-infected progressors and viremic controllers.

Brief Report: CD52 Expression on CD4+ T Cells in HIV-Positive Individuals on cART.

Background: HIV persists in a latent state in quiescent CD4 T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4 T cells in HIV-positive individuals and the impact of initiation of combination antiretroviral therapy (cART).

Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial.

The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets, determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age.

Tryptophan catabolism and immune activation in primary and chronic HIV infection.

Background: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation.

Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals.

Optimal CD4+ T cell recovery after initiating combination antiretroviral treatment (cART) in HIV infection reduces risk of morbidity and mortality. T-allele homozygosity ('TT') in the single nucleotide polymorphism, rs6897932(C/T), in the IL-7 receptor α (IL-7RA) is associated with faster CD4+ T cell recovery after cART initiation compared to C-allele homozygosity in rs6897932 ('CC'). However, underlying mechanisms are unknown.

Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin.

Background: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cells homeostatic polyclonal proliferation and regulates Th17/regulatory T-cell balance, immunological functions known to be affected during primary HIV infection.

Reduced IL-7R T Cell Expression and Increased Plasma sCD127 in Late Presenting HIV-Infected Individuals.

Background: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART.

Immune regulation in chronic hepatitis C virus infection.

The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs.

Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia.

Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng/kg) was administered intravenously in 15 healthy volunteers.

T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen.

Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection.

T cell subsets in human airways prior to and following endobronchial administration of endotoxin.

Background And Objectives: Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to determine whether pro- and anti-inflammatory T cells are involved in the local immune response to lung inflammation.

Methods: Bronchoalveolar lavage (BAL) was performed in 15 healthy volunteers, after which Escherichia coli LPS (4 ng/kg) was administered.

No association between rs6897932 in the gene encoding interleukin-7 receptor α and low-grade inflammation or self-reported health - results from the Danish Blood Donor Study.

The T-allele in the single nucleotide polymorphism rs6897932 in the gene encoding the IL-7 receptor α (IL7RA) is associated with reduced risk of autoimmune diseases including multiple sclerosis and also affects the course of HIV infection. Low-grade inflammation (LGI) and self-reported, health-related quality of life (HRQL) are often associated with chronic diseases and widely used in assessing and monitoring health status. The aim of the present study was to evaluate whether the T-allele in rs6897932 is associated with reduced risk of LGI (hsCRP 3-10 mg/L), history of infectious mononucleosis (IM), and HRQL in healthy individuals.

HIV-specific ADCC improves after antiretroviral therapy and correlates with normalization of the NK cell phenotype.

Background: Natural killer (NK) cell phenotype and function have recently gained much attention as playing crucial roles in antibody-dependent cellular cytotoxicity (ADCC). We investigated NK cell function, as measured by ADCC, in HIV-1-positive individuals before and 6 months after highly active antiretroviral therapy (HAART) initiation.

Method: The ability of antibodies and NK cells to mediate ADCC was investigated separately and in combination in an autologous model.

Polymorphism in interleukin-7 receptor α gene is associated with faster CD4⁺ T-cell recovery after initiation of combination antiretroviral therapy.

Objectives: To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor α (IL7RA) as predictors for CD4⁺ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites.

Design: SNPs in IL7RA were determined in the Danish HIV Cohort Study.

Methods: CD4⁺ T-cell changes were estimated 6 months, 1, 2, and 5 years after initiation of cART in 1683 HIV-infected virally suppressed individuals.

Regulatory T cells in HIV-infected immunological nonresponders are increased in blood but depleted in lymphoid tissue and predict immunological reconstitution.

Background: HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3 cells in lymphoid tissue, and the impact of Tregs on immunological reconstitution was determined.

Immunoregulatory T cells may be involved in preserving CD4 T cell counts in HIV-infected long-term nonprogressors and controllers.

Background: HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell counts in controllers and in LTNPs.

Different immunological phenotypes associated with preserved CD4+ T cell counts in HIV-infected controllers and viremic long term non-progressors.

Background: HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell counts in controllers and LTNP.

Polymorphisms in the interleukin-7 receptor α gene and mortality in untreated HIV-infected individuals.

Objectives: Recently, polymorphisms in the gene encoding the interleukin-7 receptor α (IL7Rα) have been shown to influence the CD4 cell count in HIV-infected individuals. The objective of this study was to examine the impact of 10 single nucleotide polymorphisms (SNPs) in or in close proximity to the IL7Rα on mortality among 152 untreated HIV infected in a Zimbabwean cohort.

Methods: Patients were followed prospectively, median time of follow-up 3.