Unraveling IFN-I response dynamics and TNF crosstalk in the pathophysiology of systemic lupus erythematosus.

Introduction: The innate immune system serves the crucial first line of defense against a wide variety of potential threats, during which the production of pro-inflammatory cytokines IFN-I and TNFα are key. This astonishing power to fight invaders, however, comes at the cost of risking IFN-I-related pathologies, such as observed during autoimmune diseases, during which IFN-I and TNFα response dynamics are dysregulated. Therefore, these response dynamics must be tightly regulated, and precisely matched with the potential threat.

Exploring the perspective of patients with immune-mediated inflammatory diseases and care providers on the use of immunomodulatory drugs in infections: an interview study.

Objectives: Immunomodulatory agents are safe and effective as treatment for various immune-mediated inflammatory diseases (IMIDs), but are associated with a slightly increased infection risk. It is uncertain whether, in the event of an infection, continuation or temporary interruption of immunomodulatory agents leads to better outcomes. Owing to this uncertainty, it is of importance to explore the perspectives of health-care providers (HCPs) and patients on this topic.

Treat-to-target in rheumatoid arthritis: a real-world study of the application and impact of treat-to-target within the wider context of patient management, patient centricity and advanced therapy use in Europe.

Background: While treat-to-target (T2T) is endorsed for the management of rheumatoid arthritis (RA), data on the degree of implementation in clinical practice are limited. This study investigated the use of T2T for RA in a real-world setting across Europe.

Methods: The Adelphi RA Disease-Specific Programme was a point-in-time survey of rheumatologists and their consulting patients with RA conducted between January and October 2020 in Belgium, France, Germany, Italy, Spain and the UK.

Identification of Risk Factors for COVID-19 Hospitalization in Patients With Anti-Rheumatic Drugs: Results From a Multicenter Nested Case Control Study.

Patients with inflammatory rheumatic diseases (IRDs) do not have an increased risk for coronavirus disease 2019 (COVID-19) compared with the general population. However, it remains uncertain whether subgroups of patients with IRD using different immunosuppressive antirheumatic drugs carry a higher risk for severe COVID-19 compared with other patients with IRD. The aim of this study is to identify risk factors for severe COVID-19, requiring hospitalization in patients with IRD.

The immunologic etiology of psychiatric manifestations in systemic lupus erythematosus: A narrative review on the role of the blood brain barrier, antibodies, cytokines and chemokines.

Introduction: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE).

Methods: A systematic search on PubMed was conducted. English studies with full text availability that investigated the correlation between blood-brain barrier (BBB) dysfunction, intrathecal synthesis of antibodies, antibodies, cytokines, chemokines, metalloproteinases, complement and psychiatric NPSLE manifestations in adults were included.

Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology.

The introduction of biologic DMARDs into rheumatology has resulted in a substantial reduction of the burden of many rheumatic diseases. In the slipstream of the success achieved with these biologic DMARDs, some conventional immunosuppressive drugs have also found use in new indications. Notably, mycophenolate mofetil, azathioprine and tacrolimus have made their way from solid organ transplantation drugs to become useful assets in rheumatology practice.

Quantification of Double Stranded DNA Breaks and Telomere Length as Proxies for Corneal Damage and Replicative Stress in Human Keratoconus Corneas.

Purpose: The pathogenesis of keratoconus (KC) is multifactorial, and associated with oxidative stress and subsequent DNA damage. We investigate differences in DNA damage and replicative stress in patients with KC, and in healthy and diseased controls.

Methods: We obtained 64 corneal buttons from 27 patients with KC after corneal transplant surgery, 21 with a decompensated graft (DG), and 16 healthy controls (HC).

B-cells and schizophrenia: A promising link or a finding lost in translation?

Recent genetic studies have suggested a potential role for B-cells in the pathogenesis of schizophrenia. Greater insight in the functioning of B-cells in patients with schizophrenia is therefore of importance. In this narrative review we aim to give an overview of the current literature on B-cells and schizophrenia.

mTOR inhibition by metformin impacts monosodium urate crystal-induced inflammation and cell death in gout: a prelude to a new add-on therapy?

Objective: Gout is the most common inflammatory arthritis worldwide, and patients experience a heavy burden of cardiovascular and metabolic diseases. The inflammation is caused by the deposition of monosodium urate (MSU) crystals in tissues, especially in the joints, triggering immune cells to mount an inflammatory reaction. Recently, it was shown that MSU crystals can induce mechanistic target of rapamycin (mTOR) signalling in monocytes encountering these crystals in vitro.

PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation.

Chronic inflammatory diseases are characterized by recurrent inflammatory attacks in the tissues mediated by autoreactive T cells. Identity and functional programming of CD8+ T cells at the target site of inflammation still remain elusive. One key question is whether, in these antigen-rich environments, chronic stimulation leads to CD8+ T cell exhaustion comparable to what is observed in infectious disease contexts.

Telomere quantification in frontal and temporal brain tissue of patients with schizophrenia.

Recent imaging studies have suggested that accelerated aging occurs in schizophrenia. However, the exact cause of these findings is still unclear. In this study we measured telomere length, a marker for cell senescence, in gray and white matter brain tissue from the medial frontal gyrus (MFG) and superior temporal gyrus (STG) of 9 patients with schizophrenia and 11 controls.

Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?

Background: Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its anti-inflammatory properties.

Objective: To provide a critical and comprehensive review of the available literature describing the effects of metformin on the immune system and on auto-inflammatory diseases.

Results: Based on the available scientific literature, metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production.

Association of MicroRNA-618 Expression With Altered Frequency and Activation of Plasmacytoid Dendritic Cells in Patients With Systemic Sclerosis.

Objective: Plasmacytoid dendritic cells (PDCs) are a critical source of type I interferons (IFNs) that can contribute to the onset and maintenance of autoimmunity. Molecular mechanisms leading to PDC dysregulation and a persistent type I IFN signature are largely unexplored, especially in patients with systemic sclerosis (SSc), a disease in which PDCs infiltrate fibrotic skin lesions and produce higher levels of IFNα than those in healthy controls. This study was undertaken to investigate potential microRNA (miRNA)-mediated epigenetic mechanisms underlying PDC dysregulation and type I IFN production in SSc.

Aberrant leukocyte telomere length in Birdshot Uveitis.

Purpose: Birdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout.

Aim And Background: Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout.

Methods: We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New Zealand.

The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: a multicentre European Scleroderma Trials and Research group (EUSTAR) study.

Objectives: The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/or SSc-related organ involvement.

Methods: Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group.

Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids.

Objectives: Glucocorticoids (GC) remain a cornerstone of rheumatoid arthritis (RA) therapy, although a third of patients do not respond adequately. In order to find potential predictors for clinical response, the gene expression profile of CD4+T-cells as important players in the pathogenesis of RA was analysed before pulse therapy with 1000 mg methylprednisolone.

Methods: Patients were treated with 3x1000 mg methylprednisolone in 5 days; hereafter response was determined by the European League Against Rheumatism (EULAR) response criteria.

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells.

The generation of naive T cells is dependent on thymic output, but in adults, the naive T cell pool is primarily maintained by peripheral proliferation. Naive T cells have long been regarded as relatively quiescent cells; however, it was recently shown that IL-8 production is a signatory effector function of naive T cells, at least in newborns. How this functional signature relates to naive T cell dynamics and aging is unknown.

A Promoter Polymorphism in the CD59 Complement Regulatory Protein Gene in Donor Lungs Correlates With a Higher Risk for Chronic Rejection After Lung Transplantation.

Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription.

Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin-8 (CXCL8), Myeloid-Related Protein 8/Myeloid-Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease.

Objective: The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients.

Methods: We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls.