Dengue NS1 induces phospholipase A enzyme activity, prostaglandins, and inflammatory cytokines in monocytes.

Introduction: Dengue virus (DENV) NS1 is a non-structural secretory protein associated with severe disease and known to cause vascular leak leading to dengue haemorrhagic fever (DHF). As phospholipases A (PLA) enzymes, platelet activating factor, and leukotrienes are elevated in dengue, we sought to investigate whether NS1 potentially contributes to disease pathogenesis by inducing PLAs.

Methods: THP-1 cells and primary human monocytes of healthy adults (n = 6) were co-cultured with DENV1 NS1, LPS and media alone.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis.

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis.

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis.

Objective: To develop and validate classification criteria for microscopic polyangiitis (MPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis.

Objective: To develop and validate classification criteria for microscopic polyangiitis (MPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis.

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis With Polyangiitis.

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

Association of dengue virus-specific polyfunctional T-cell responses with clinical disease severity in acute dengue infection.

Introduction: Although the role of dengue virus (DENV)-specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus-specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV-NS3 and DENV-NS5 protein-specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF).

Methods: Using intracellular cytokine assays, we assessed the production of interferon γ (IFNγ), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β), and CD107a expression in adult patients with acute DF (n = 21) and DHF (n = 22).

Altered monocyte response to the dengue virus in those with varying severity of past dengue infection.

Objective: We sought to investigate the differences in monocyte immune responses to the dengue virus (DENV) in those who previously had either severe disease (past SD) or non-severe dengue (past NSD) following a secondary dengue infection.

Method: Monocytes from healthy individuals who had either past SD (n = 6) or past NSD (n = 6) were infected at MOI one with all four DENV serotypes following incubation with autologous serum. 36-hours post infection, levels of inflammatory cytokines and viral loads were measured in the supernatant and expression of genes involved in viral sensing and interferon signaling was determined.

Patterns and causes of liver involvement in acute dengue infection.

Background: Liver involvement in acute dengue infection is frequently observed and sometimes leads to acute liver failure, with fatal outcomes. Many factors are thought to contribute to liver dysfunction, including hypoxic injury due to decreased perfusion, direct damage by the virus and immune mediated injury. In this study, we sought to identify the pattern in the change in liver enzymes throughout the illness and its association with the degree of viraemia, onset and extent of plasma leakage and inflammatory mediators.

Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka.

Background: Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka.

Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection.

Background: Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood.

Methodology/principal Findings: Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides.

Sphingosine 1-phosphate in acute dengue infection.

Background: Vascular leak is the hallmark of severe dengue infections and leads to complications such as shock and multi-organ failure. Although many mediators have been implicated in the vascular leak in dengue, the role of sphingosine 1-phosphate (S1P) has not been investigated.

Metholodology/principal Findings: As S1P has been shown to be important in barrier integrity, we assessed the S1P levels in 28 patients with acute dengue and 12 healthy individuals.

T cell responses in dengue viral infections.

Dengue viral infections are the commonest mosquito borne viral infection in the world, affecting more than 100 countries and 390 million individuals annually. Currently, there are no effective antiviral drugs or an effective vaccine to prevent infection. A main hurdle in developing a safe and effective vaccine has been our poor understanding of the complex nature of the protective immune response in acute dengue infection and the presence of four dengue virus (DV) serotypes that are highly homologous.