Paucity of viral infection symptoms in patients with immune-mediated inflammatory diseases.

Objectives: Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.

Design: A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.

Identification of red flags for IgG4-related disease: an international European Reference Network for Rare Connective Tissue Diseases framework.

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease.

CD19-CAR T-cell therapy induces deep tissue depletion of B cells.

Objectives: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.

Methods: Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs.

Anatomical pattern of entheseal and synovial fibroblast activation in patients with psoriasis and its risk of developing psoriatic arthritis.

Objectives: To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by gallium-labelled fibroblast activation protein inhibitor-04 (Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).

Methods: We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with Ga-FAPI-04. Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings.

Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.

Transforming growth factor β (TGF-β) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-β remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-β in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-β.

Fibroblast Activation Protein (FAP)-Mediated Cleavage of Type III Collagen Reveals Serum Biomarker Potential in Non-Small Cell Lung Cancer and Spondyloarthritis.

Fibroblast activation protein (FAP) is a known promoter of tumor development and is associated with poor clinical outcome for various cancer types. Being specifically expressed in pathological conditions including multiple types of fibrosis and cancers, FAP is an optimal target for diagnostics and treatment. Treatment strategies utilizing the unique proteolytic activity of FAP are emerging, thus emphasizing the importance of biomarkers to directly assess FAP activity.

CD200 fibroblasts form a pro-resolving mesenchymal network in arthritis.

Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition.

GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci.

Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection.

In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection.

Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival: A Large Cohort Study of the German Network for Systemic Sclerosis.

Background: Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis.

Research Question: Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact?

Study Design And Methods: Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry.

Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis.

Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and the initial response of microglia determines the severity of neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate the activation status of dendritic cells and macrophages. Although the expression of CD83 is associated with early microglia activation in various disease settings, its functional relevance for microglial biology has been elusive.

Student-led clinics and ePROs to accelerate diagnosis and treatment of patients with axial spondyloarthritis: results from a prospective pilot study.

We aimed to investigate (1) student-led clinics and (2) electronic patient-reported outcomes (ePROs) to accelerate diagnosis and treatment of patients with axial spondyloarthritis (axSpA). Patients with suspected axSpA completed an initial student-led clinic visit (T-1) prior to their planned actual rheumatologist visit (T0). Acceleration of patient appointment and NSAID therapy start, availability of diagnostic findings, and treatment response at T0 were evaluated.

Stepwise asynchronous telehealth assessment of patients with suspected axial spondyloarthritis: results from a pilot study.

Patients with axial spondyloarthritis (axSpA) suffer from one of the longest diagnostic delays among all rheumatic diseases. Telemedicine (TM) may reduce this diagnostic delay by providing easy access to care. Diagnostic rheumatology telehealth studies are scarce and largely limited to traditional synchronous approaches such as resource-intensive video and telephone consultations.

Anti-acid therapy in SSc-associated interstitial lung disease: long-term outcomes from the German Network for Systemic Sclerosis.

Objectives: Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD).

Methods: We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards).

Deep Tissue Characterization with Optical Coherence Elastography: A Comparison of Different Methods.

The measurement of the biomechanical properties of the skin is of great interest since these properties play an important role in the development of several diseases such as skin cancer and systemic sclerosis. In this direction, several diagnostic tools have been developed to analyze the mechanical properties of the skin. Optical coherence elastography (OCE) is one of the emerging imaging techniques used for the characterization of the mechanical properties of the tissue quantitatively.

Fibroblast Activation Protein Inhibitor Imaging in Nonmalignant Diseases: A New Perspective for Molecular Imaging.

Fibroblast activation protein-α (FAP-α) is a type II transmembrane glycoprotein that is overexpressed in activated fibroblasts such as those in the stroma of tumors or in the fibrotic processes accompanying various benign diseases. The recent development and clinical implementation of radiolabeled quinolone-based tracers suitable for PET that act as FAP inhibitors (FAPIs) have opened a new perspective in molecular imaging. Although multiple studies have investigated the use of FAPI imaging in cancer, evidence concerning its use in nonmalignant diseases is still scarce.