Reduced IFNL1 and/or IFNL2, but not IFNL3 is associated with worse outcome in patients with COVID-19.

The recent pandemic was caused by the emergence of a new human pathogen, SARS-CoV-2. While the rapid development of many vaccines provided an end to the immediate crisis, there remains an urgent need to understand more about this new virus and what constitutes a beneficial immune response in terms of successful resolution of infection. Indeed, this is key for development of vaccines that provide long lasting protective immunity.

Profound and selective lymphopaenia in primary lymphatic anomaly patients demonstrates the significance of lymphatic-lymphocyte interactions.

Introduction: The lymphatic system has a pivotal role in immune homeostasis. To better understand this, we investigated the impact of Primary Lymphatic Anomalies (PLA) on lymphocyte numbers and phenotype.

Methods: The study comprised (i) a retrospective cohort: 177 PLA subjects from the National Primary Lymphatic Anomaly Register with clinical and laboratory data, and (ii) a prospective cohort: 28 patients with PLA and 20 healthy controls.

Chromoblastomycosis Treated With Posaconazole and Adjunctive Imiquimod: Lending Innate Immunity a Helping Hand.

Chromoblastomycosis (CBM) is a difficult-to-treat, chronic fungal infection of the skin and subcutaneous tissue. The evidence base for treatment is scarce, with no standardized therapeutic approach. Chronicity of CBM infection is postulated to be due in part to a failure of host cell-mediated immunity to generate a proinflammatory response sufficient for fungal clearance.

'We want it all': ART preferences assessed by Desirability of Outcome Ranking.

Objectives: Understanding how people living with HIV (PLWH) view antiretroviral therapy (ART) prescribing choices is fundamental to patient-centred care. We used the Desirability of Outcome Ranking (DOOR) approach to explore patient ART preferences.

Methods: Seventy-four PLWH entered the study, 20 into the 'pilot study', and 54 in the 'comparative study'.

Increased monocyte distribution width in COVID-19 and sepsis arises from a complex interplay of altered monocyte cellular size and subset frequency.

Introduction: Monocyte distribution width (MDW), a parameter generated alongside full blood counts (FBC) in new-generation haematology analysers, has been proposed as a diagnostic test for severe infection/sepsis. It represents the standard deviation (SD) of the monocyte mean volume (MMV).

Methods: This study aimed to compare monocyte volumetric parameters retrieved by the UniCel DxH 900 haematology analyser (MMV and MDW) against corresponding parameters from the same sample measured using flow cytometry (forward scatter [FSC] mean and SD) in combination with phenotypic characterization of monocyte subtypes.

Identification of proliferative and non-proliferative subpopulations of leukemic cells in CLL.

Pathogenesis in chronic lymphocytic leukemia (CLL) is strongly linked to the potential for leukemic cells to migrate to and proliferate within lymph-nodes. Previous in vivo studies suggest that all leukemic cells participate in cycles of migration and proliferation. In vitro studies, however, have shown heterogeneous migration patterns.

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes.

Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.

Background: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (arts, mmunodeficiency, ymphoedema and anogenital ysplasia), have previously depended on a single case report.

Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.

CD57 Memory T Cells Proliferate In Vivo.

A central paradigm in the field of lymphocyte biology asserts that replicatively senescent memory T cells express the carbohydrate epitope CD57. These cells nonetheless accumulate with age and expand numerically in response to persistent antigenic stimulation. Here, we use in vivo deuterium labeling and ex vivo analyses of telomere length, telomerase activity, and intracellular expression of the cell-cycle marker Ki67 to distinguish between two non-exclusive scenarios: (1) CD57 memory T cells do not proliferate and instead arise via phenotypic transition from the CD57 memory T cell pool; and/or (2) CD57 memory T cells self-renew via intracompartmental proliferation.

Images of the month: Cavernous sinus venous thrombosis secondary to maxillary sinusitis: An unusual cause of diplopia and headache.

Cavernous sinus venous thrombosis is an uncommon condition associated with high mortality rates if not recognised early. Symptoms include headache, visual loss, ophthalmoplegia, altered consciousness, proptosis and periorbital oedema. High-quality imaging is critical in early diagnosis and successful management.

Presentations and outcomes of central nervous system TB in a UK cohort: The high burden of neurological morbidity.

Objectives: Most data for Central Nervous System Tuberculosis (CNS-TB) derive from high-incidence, resource-limited countries. We sought to determine the presentation, management and outcomes of CNS-TB in a low-incidence setting with accessible healthcare.

Methods: We undertook a retrospective, observational study of CNS-TB in adults at a single tertiary-referral London hospital (2001-2017).

The Rules of Human T Cell Fate .

The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells , lymphocyte fate is age-dependent and that younger cells (i.e.

Current estimates of T cell kinetics in humans.

Stable isotope labeling is a generally applicable method of quantifying cell dynamics. Its advent has opened up the way for the quantitative study of T cells in humans. However, the literature is confusing as estimates vary by orders of magnitude between studies.

Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study.

Background: The clinical utility of interferon-γ release assays (IGRAs) for diagnosis of active tuberculosis is unclear, although they are commonly used in countries with a low incidence of tuberculosis. We aimed to resolve this clinical uncertainty by determining the accuracy and utility of commercially available and second-generation IGRAs in the diagnostic assessment of suspected tuberculosis in a low-incidence setting.

Methods: We did a prospective cohort study of adults with suspected tuberculosis in routine secondary care in England.

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 T cell-mediated control of HIV-1, HCV, and HTLV-1.

Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8 T cell survival.

Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.

Adaptive immunity relies on the generation and maintenance of memory T cells to provide protection against repeated antigen exposure. It has been hypothesised that a self-renewing population of T cells, named stem cell-like memory T (TSCM) cells, are responsible for maintaining memory. However, it is not clear if the dynamics of TSCM cells in vivo are compatible with this hypothesis.

Murine IL-4Δ2 splice variant down-regulates IL-4 activities independently of IL-4Rα binding and STAT-6 phosphorylation.

IL-4 is a pleiotropic cytokine that is highly Th2 polarizing. The ratio of IL-4 and its splice variant IL-4Δ2 observed in human health and disease suggests a role for both isoforms. In the present study, the biological function of murine IL-4Δ2 and the potential mechanism of action were studied.

The fate and lifespan of human monocyte subsets in steady state and systemic inflammation.

In humans, the monocyte pool comprises three subsets (classical, intermediate, and nonclassical) that circulate in dynamic equilibrium. The kinetics underlying their generation, differentiation, and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses. Here, using human in vivo deuterium labeling, we demonstrate that classical monocytes emerge first from marrow, after a postmitotic interval of 1.

Physiologically Based Simulations of Deuterated Glucose for Quantifying Cell Turnover in Humans.

[6,6-H]-glucose labeling is a state-of-the-art technique for quantifying cell proliferation and cell disappearance in humans. However, there are discrepancies between estimates of T cell proliferation reported in short (1-day) versus long (7-day) H-glucose studies and very-long (9-week) HO studies. It has been suggested that these discrepancies arise from underestimation of true glucose exposure from intermittent blood sampling in the 1-day study.