Prospective registration of trials: where we are, why, and how we could get better.

Objectives: Transparent trial conduct requires prospective registration of a randomized controlled clinical trial (RCT) before the enrollment of the first participant. We aimed to (1) estimate the proportion of RCTs that are prospectively registered and analyze the time trends and factors linked to registration timing and (2) assess the reasons for nonadherence to prospective registration and explore ways to improve compliance. We studied trials published in rheumatology as a case study.

Anti-apolipoprotein A-1 IgG, incident cardiovascular events, and lipid paradox in rheumatoid arthritis.

Objective: To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale.

Method: Baseline AAA1 IgG, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1,472 patients with RA included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years.

The autoinflammation-associated NLRC4 mutation increases microbiota-independent IL-18 production but does not recapitulate human autoinflammatory symptoms in mice.

Background: Autoinflammation with infantile enterocolitis (AIFEC) is an often fatal disease caused by gain-of-function mutations in the NLRC4 inflammasome. This inflammasomopathy is characterized by macrophage activation syndrome (MAS)-like episodes as well as neonatal-onset enterocolitis. Although elevated IL-18 levels were suggested to take part in driving AIFEC pathology, the triggers for IL-18 production and its ensuing pathogenic effects in these patients are incompletely understood.

Immunosuppression is a conserved driver of tuberculosis susceptibility.

( ) causes 1.6 million deaths a year . However, no individual mouse model fully recapitulates the hallmarks of human tuberculosis disease.

Regulatory T cell-derived IL-1Ra suppresses the innate response to respiratory viral infection.

Regulatory T (T) cell modulation of adaptive immunity and tissue homeostasis is well described; however, less is known about T cell-mediated regulation of the innate immune response. Here we show that deletion of ST2, the receptor for interleukin (IL)-33, on T cells increased granulocyte influx into the lung and increased cytokine production by innate lymphoid and γδ T cells without alteration of adaptive immunity to influenza. IL-33 induced high levels of the interleukin-1 receptor antagonist (IL-1Ra) in ST2 T cells and deletion of IL-1Ra in T cells increased granulocyte influx into the lung.

Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care.

Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018.

Targeted removal of macrophage-secreted interleukin-1 receptor antagonist protects against lethal Candida albicans sepsis.

Invasive fungal infections are associated with high mortality rates, and the lack of efficient treatment options emphasizes an urgency to identify underlying disease mechanisms. We report that disseminated Candida albicans infection is facilitated by interleukin-1 receptor antagonist (IL-1Ra) secreted from macrophages in two temporally and spatially distinct waves. Splenic CD169 macrophages release IL-1Ra into the bloodstream, impeding early neutrophil recruitment.

The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis.

Background: Interleukin-18 is a proinflammatory cytokine, the activity of which is regulated by its natural inhibitor, IL-18 binding protein (IL-18BP). Elevated circulating levels of IL-18 have been observed in patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), two conditions associated with dysregulated innate immune responses. This study examines the expression and function of IL-18 and IL-18BP in K/BxN serum transfer arthritis (STA), a model that is uniquely dependent on innate immune responses.

Detection of Free Bioactive IL-18 and IL-18BP in Inflammatory Disorders.

The interleukin (IL)-18 cytokine plays an important driver role in a range of autoimmune and inflammatory diseases, as well as cancer. IL-18 is a potent inducer of interferon gamma (IFN-γ), and the bioactivity of IL-18 is regulated by its natural soluble inhibitor, IL-18-binding protein (IL-18BP), which is present at high concentrations in the circulation. Many cell types have been described to secrete IL-18BP, constitutively or under the influence of IFN-γ, thus generating a negative feedback loop for IL-18.

Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases.

Objectives: To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients.

Methods: This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included.

IL-18 Binding Protein-Producing Cells Attenuate Anemia in Murine Macrophage Activation Syndrome.

IL-18 is a pleiotropic immunoregulatory cytokine of the IL-1 family. IL-18 has been identified as a potent IFN-γ inducer in synergy with IL-12 and IL-15 and thus as a powerful Th1 cell-polarizing cytokine. IL-18 activity is regulated by its naturally occurring soluble inhibitor IL-18 binding protein (IL-18BP), the production of which is stimulated by IFN-γ in a negative feedback loop.

The cytosolic DNA sensor AIM2 promotes Helicobacter-induced gastric pathology via the inflammasome.

Helicobacter pylori (H. pylori) infection can trigger chronic gastric inflammation perpetuated by overactivation of the innate immune system, leading to a cascade of precancerous lesions culminating in gastric cancer. However, key regulators of innate immunity that promote H.

Reporting and Representativeness of Race, Ethnicity, and Socioeconomic Status in Systemic Sclerosis Randomized Trials: An Observational Study.

Objective: To assess how and to what extent socioeconomic status and ethnicity/race of participants are reported in randomized controlled trials (RCTs) on systemic sclerosis (SSc), and to estimate the representativeness of different ethnic/racial groups in SSc RCTs.

Methods: We searched all published RCTs on SSc indexed in PubMed. We retrieved information on main features of RCTs published from 2000 onward and recorded for each study whether race/ethnicity was reported; how ethnicity/race was defined and assigned; and the number of patients included for each racial/ethnic group.

Cross-talk between IL-6 trans-signaling and AIM2 inflammasome/IL-1β axes bridge innate immunity and epithelial apoptosis to promote emphysema.

Pulmonary emphysema is associated with dysregulated innate immune responses that promote chronic pulmonary inflammation and alveolar apoptosis, culminating in lung destruction. However, the molecular regulators of innate immunity that promote emphysema are ill-defined. Here, we investigated whether innate immune inflammasome complexes, comprising the adaptor ASC, Caspase-1 and specific pattern recognition receptors (PRRs), promote the pathogenesis of emphysema.

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update.

Background: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway.

Management of hand osteoarthritis: from an US evidence-based medicine guideline to a European patient-centric approach.

Hand osteoarthritis is the most common joint condition and is associated with significant morbidity. It is of paramount importance that patients are thoroughly assessed and examined when complaining of hand stiffness, pain, deformity or disability and that the patient's concerns and expectations are addressed by the healthcare professional. In 2019 the American College of Rheumatology and Arthritis Foundation (ACR/AF) produced guidelines which included recommendations for the treatment of hand osteoarthritis.

Long-term persistence of antibodies after diphtheria/tetanus vaccination in immunosuppressed patients with inflammatory rheumatic diseases and healthy controls.

Many vaccines demonstrate high effectiveness for years. This prospective multicentre study was conducted in Switzerland to assess the long-term persistence of antibodies to the diphtheria/tetanus (dT)-vaccine in adult patients with rheumatic diseases (PRDs). 163 PRDs and 169 controls were included in the study.

Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling.

Objectives: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.

Methods: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC.

Structural basis of human IL-18 sequestration by the decoy receptor IL-18 binding protein in inflammation and tumor immunity.

Human Interleukin-18 (IL-18) is an omnipresent proinflammatory cytokine of the IL-1 family with central roles in autoimmune and inflammatory diseases and serves as a staple biomarker in the evaluation of inflammation in physiology and disease, including the inflammatory phase of COVID-19. The sequestration of IL-18 by its soluble decoy receptor IL-18-Binding Protein (IL-18BP) is critical to the regulation of IL-18 activity. Since an imbalance in expression and circulating levels of IL-18 is associated with disease, structural insights into how IL-18BP outcompetes binding of IL-18 by its cognate cell-surface receptors are highly desirable; however, the structure of human IL-18BP in complex with IL-18 has been elusive.