Pharmacological inhibition of MutT homolog 1 (MTH1) in allergic airway inflammation as a novel treatment strategy.

Background: Despite progress in the treatment of asthma, there is an unmet need for additional therapeutic strategies, not least to avoid side-effects of corticosteroids. The enzyme MutT homolog 1 (MTH1) hydrolyzes oxidized purines and prevents their insertion to DNA. Small molecule inhibition of MTH1 has shown promising therapeutic effects in both cancer and inflammatory conditions.

Synovial fibroblasts from children with oligoarticular juvenile idiopathic arthritis induce migration and prolong viability of neutrophils.

Introduction: Little is known of the processes that trigger neutrophil activation in the joint of patients with oligoarticular juvenile idiopathic arthritis (oJIA), and if synovial fibroblasts (S-Fib) play an important role in the activation. Therefore, we aimed to investigate whether S-Fib derived from oJIA patients drive neutrophil activation.

Methods: Synovial fluid (SF) was collected from patients with oJIA.

Capillary leak syndrome was associated with more severe multisystem inflammatory syndrome in children during the COVID-19 pandemic.

Aim: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity.

Methods: All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied.

Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions.

Introduction: Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features.

Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD CAA prevention (KD-CAAP) trial protocol.

Background: Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD.

Identification of novel autoantigens as potential biomarkers in juvenile idiopathic arthritis associated uveitis.

Background: Many children with juvenile idiopathic arthritis (JIA) have autoantibodies, targeting nuclear components (anti-nuclear antibodies, ANA). ANA in JIA is associated with uveitis, an eye inflammation which may cause permanent vision impairment if not detected and treated. However, ANA-testing is neither specific nor sensitive enough to be a clinically reliable predictor of uveitis risk, and the precise autoantigens targeted by ANA in JIA are largely unknown.

The risk of depression and anxiety is not increased in individuals with juvenile idiopathic arthritis - results from the south-Swedish juvenile idiopathic arthritis cohort.

Background: Children with chronic diseases are reported to have increased risk of psychiatric comorbidity. Few studies have investigated this risk in juvenile idiopathic arthritis (JIA), with conflicting results. We performed a population-based, longitudinal cohort study of the risk of depression and anxiety in south-Swedish patients with juvenile arthritis.

Risk factors for multisystem inflammatory syndrome in children - A population-based cohort study of over 2 million children.

Background: Although severe acute COVID-19 is rare in children, SARS-CoV-2 infection can trigger the novel post-infectious condition multisystem inflammatory syndrome in children (MIS-C). Increased knowledge on risk factors for MIS-C could improve our understanding of the pathogenesis of the condition and better guide targeted public health interventions. The aim of the study was to assess risk factors for MIS-C with the aim to identify vulnerable children.

Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus.

Background:  Systemic lupus erythematosus (SLE) is a complex disease characterized by autoimmunity toward apoptotic cells, excessive amounts of circulating immune complexes, and complement activation. A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome.

Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes.

Sepsis manifests due to the host's dysregulated immune response to infection. High-dose ascorbic acid (AA) has emerged as a potential treatment of sepsis, yet little is known regarding how AA influences the immune system in sepsis, such as monocytes. The objective of this study is to investigate the effects of high-dose AA on monocyte polarization and cytokine production in vitro.

Neutrophils Lose the Capacity to Suppress T Cell Proliferation Upon Migration Towards Inflamed Joints in Juvenile Idiopathic Arthritis.

Neutrophils are highly abundant in synovial fluid of rheumatic inflamed joints. In oligoarticular juvenile idiopathic arthritis (JIA), synovial fluid neutrophils have impaired effector functions and altered phenotype. We hypothesized that these alterations might impact the immunoregulatory interplay between neutrophils and T cells.

Ligand-Independent G Protein-Coupled Estrogen Receptor/G Protein-Coupled Receptor 30 Activity: Lack of Receptor-Dependent Effects of G-1 and 17-Estradiol.

G protein-coupled receptor 30 (GPR30) is a membrane receptor reported to bind 17-estradiol (E2) and mediate rapid nongenomic estrogen responses, hence also named G protein-coupled estrogen receptor. G-1 is a proposed GPR30-specific agonist that has been used to implicate the receptor in several pathophysiological events. However, controversy surrounds the role of GPR30 in G-1 and E2 responses.

Synovial fluid neutrophils in oligoarticular juvenile idiopathic arthritis have an altered phenotype and impaired effector functions.

Background: Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize the phenotype and function of synovial fluid neutrophils in oligoarticular JIA.

High risk of coronary artery aneurysm in Kawasaki disease.

Objective: Kawasaki disease (KD) is a vasculitis of unknown aetiology with a high risk of coronary aneurysms if untreated. Timely treatment with intravenous immunoglobulin decreases the risk for coronary artery aneurysms (CAA). In this study, we set out to elucidate the factors associated with the risk of developing CAA.

Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19.

The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines.

Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment-a distinct inflammatory pattern for oligoarticular juvenile arthritis.

Background: Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied.

Outcome in juvenile idiopathic arthritis: a population-based study from Sweden.

Background: As the treatment arsenal for children with juvenile idiopathic arthritis (JIA) has expanded during the last decades, follow-up studies are needed on children diagnosed in the era of biological treatment to evaluate if this has improved the outcome. Our aim was to study the epidemiology and outcome of JIA in southern Sweden using a population-based cohort of children with a validated diagnosis of JIA collected over 9 years.

Methods: Potential cases of JIA between 2002 and 2010 were collected after a database search, using the ICD codes M08-M09.

Blockade of the kallikrein-kinin system reduces endothelial complement activation in vascular inflammation.

Background: The complement and kallikrein-kinin systems (KKS) are activated during vascular inflammation. The aim of this study was to investigate if blockade of the KKS can affect complement activation on the endothelium during inflammation.

Methods: Complement deposition on endothelial microvesicles was assayed in vasculitis patient plasma samples and controls.

Heparin-Binding Protein as a Prognostic Biomarker of Sepsis and Disease Severity at the Emergency Department.

Objective: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department.

Human G protein-coupled receptor 30 is -glycosylated and N-terminal domain asparagine 44 is required for receptor structure and activity.

G protein-coupled receptor 30 (GPR30), or G protein-coupled estrogen receptor (GPER), is a G protein-coupled receptor (GPCR) that is currently attracting considerable attention in breast cancer and cardiometabolic regulation. The receptor was reported to be a novel membrane estrogen receptor mediating rapid non-genomic responses. However, questions remain about both the cognate ligand and the subcellular localization of receptor activity.