Immunoadsorption as a novel therapy for refractory idiopathic inflammatory myopathies-a retrospective observational study.

Objective: Idiopathic inflammatory myopathies (IIM) are autoimmune disorders characterised by muscle inflammation, high creatine kinase (CK) levels, and disability. Despite immunomodulating therapies, patients often experience progressive disease, resulting in refractory conditions or dependence on glucocorticoids (GC). This study addresses the efficacy and safety of immunoadsorption (IAS) in refractory IIM.

Autoantibody development is associated with clinical severity of COVID-19: A cohort study.

Viral infections, including respiratory diseases such as Coronavirus disease 2019 (COVID-19), are hypothesized to contribute to the onset of autoimmune disorders. Although elevated levels of autoantibodies have been observed following COVID-19, the role of specific autoantibodies linked to autoimmune diseases and their correlation with disease severity remains poorly defined. In this study, we used a comprehensive autoantibody panel to assess the autoantibody production across different cohorts of COVID-19 patients, categorized by disease severity.

Ex vivo imaging-based high content phenotyping of patients with rheumatoid arthritis.

Background: High content imaging-based functional precision medicine approaches have been developed and successfully applied in the field of haemato-oncology. For rheumatoid arthritis (RA), treatment selection is still based on a trial-and-error principle, and biomarkers for patient stratification and drug response prediction are needed.

Methods: A high content, high throughput microscopy-based phenotyping pipeline for peripheral blood mononuclear cells (PBMCs) was developed, allowing for the quantification of cell type frequencies, cell type specific morphology and intercellular interactions from patients with RA (n = 65) and healthy controls (HC, n = 33).

HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections.

Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting polarization toward Th17 by restricting expression of the cytokine receptors gp130 and transforming growth factor β receptor 2 (TGF-βRII) in a fungus-specific manner, thus limiting Stat3 and Smad2/3 signaling. Controlled release of interleukin-17A (IL-17A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is vital to minimize apoptotic processes in renal tubular epithelial cells in vitro and in vivo.

Humoral and cellular response to the third COVID-19 vaccination in patients with inborn errors of immunity or mannose-binding lectin deficiency : A prospective controlled open-label trial.

Impaired immune response to COVID-19 (coronavirus disease 2019) vaccination has been reported in patients with inborn errors of immunity (IEI). Repetitive vaccinations are recommended for this vulnerable group. Due to the high diversity within IEI patients, additional safety and immunogenicity data are needed to better understand these aspects especially in less common immunodeficiency syndromes.

Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases.

Due to optimised treatment strategies and the availability of new therapies during the last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art treatment cannot induce remission. Moreover, the risk for flares strongly increases once anti-inflammatory therapy is tapered or withdrawn, suggesting that underlying pathological processes remain active even in the absence of overt inflammation.

FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study.

Background: Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using ⁶⁸Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT).

Immunogenicity and safety of COVID-19 booster vaccination: A population-based clinical trial to identify the best vaccination strategy.

Background: Various SARS-CoV-2 variants of concerns (VOCs) characterized by higher transmissibility and immune evasion have emerged. Despite reduced vaccine efficacy against VOCs, currently available vaccines provide protection. Population-based evidence on the humoral immune response after booster vaccination is crucial to guide future vaccination strategies and in preparation for imminent COVID-19 waves.

Impact of muscle biopsy on the clinical decision-making process in patients with suspected idiopathic inflammatory myopathy.

Background: The significance of muscle biopsy as a diagnostic tool in idiopathic inflammatory myopathies (IIM) remains elusive. We aimed to determine the diagnostic weight that has been given to muscle biopsy in patients with suspected IIM, particularly in terms of clinical diagnosis and therapeutic decisions.

Material And Methods: In this retrospective multicentric study, we analyzed muscle biopsy results of adult patients with suspected IIM referred to a tertiary center between January 1, 2007, and October 31, 2021.

Amino Acids Fueling Fibroblast-Like Synoviocyte Activation and Arthritis By Regulating Chemokine Expression and Leukocyte Migration.

Objective: We analyzed the impact of amino acid (AA) availability on the inflammatory response in arthritis.

Methods: We stimulated rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) with tumor necrosis factor (TNF) in the presence or absence of proteinogenic AAs and measured their response by QuantSeq 3' messenger RNA sequencing, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. Signal transduction events were determined by Western blot.

Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story.

Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatory disorders. Disease-associated immune responses typically involve a complex interplay of multiple cytokines.

The guanine nucleotide exchange factor Rin-like controls Tfh cell differentiation via CD28 signaling.

T follicular helper (Tfh) cells are essential for the development of germinal center B cells and high-affinity antibody-producing B cells in humans and mice. Here, we identify the guanine nucleotide exchange factor (GEF) Rin-like (Rinl) as a negative regulator of Tfh generation. Loss of Rinl leads to an increase of Tfh in aging, upon in vivo immunization and acute LCMV Armstrong infection in mice, and in human CD4+ T cell in vitro cultures.

Cytokine-directed cellular cross-talk imprints synovial pathotypes in rheumatoid arthritis.

Introduction: Structural reorganisation of the synovium with expansion of fibroblast-like synoviocytes (FLS) and influx of immune cells is a hallmark of rheumatoid arthritis (RA). Activated FLS are increasingly recognised as a critical component driving synovial tissue remodelling by interacting with immune cells resulting in distinct synovial pathotypes of RA.

Methods: Automated high-content fluorescence microscopy of co-cultured cytokine-activated FLS and autologous peripheral CD4 T cells from patients with RA was established to quantify cell-cell interactions.

Advanced immunophenotyping: A powerful tool for immune profiling, drug screening, and a personalized treatment approach.

Various autoimmune diseases are characterized by distinct cell subset distributions and activation profiles of peripheral blood mononuclear cells (PBMCs). PBMCs can therefore serve as an ideal biomarker material, which is easily accessible and allows for screening of multiple cell types. A detailed understanding of the immune landscape is critical for the diagnosis of patients with autoimmune diseases, as well as for a personalized treatment approach.

Accelerated waning of immune responses to a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases.

Background: A 3 COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed. Currently it remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.

Reduced immunogenicity of BNT162b2 booster vaccination in combination with a tetravalent influenza vaccination: results of a prospective cohort study in 838 health workers.

Objective: To investigate the immunogenicity and safety of BNT162b2 booster vaccination with and without a tetravalent influenza vaccine.

Methods: A prospective, open-label cohort study on immunogenicity and safety of COVID-19 booster vaccination with or without a tetravalent influenza vaccine was performed. Eight hundred thirty-eight health care workers were included in the following study arms: BNT162b2 booster-only, influenza-vaccine-only or combination of both.

[National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic DMARDS (disease modifying antirheumatic drugs)].

This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.

Multiparametric Prediction Models for Coronavirus Disease 2019 Vaccine Selection: Results of a Comparative Population-Based Cohort Study.

Background: An understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19).

Methods: In this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1).

Results: Our main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.

Reactogenicity and immunogenicity of the second COVID-19 vaccination in patients with inborn errors of immunity or mannan-binding lectin deficiency.

Background: Patients with inborn errors of immunity (IEI) are at increased risk for severe courses of SARS-CoV-2 infection. COVID-19 vaccination provides effective protection in healthy individuals. However, it remains unclear whether vaccination is efficient and safe in patients with constitutional dysfunctions of the immune system.

Safety and immunogenicity of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases compared with healthy controls.

Objectives: A third COVID-19 vaccination is recommended for immunosuppressed patients. However, data on immunogenicity and safety of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are sparse and therefore addressed within this clinical trial.

Methods: 60 immunosuppressed patients and 48 healthy controls (HCs) received a third vaccination with an mRNA vaccine.

Heterologous vector versus homologous mRNA COVID-19 booster vaccination in non-seroconverted immunosuppressed patients: a randomized controlled trial.

Impaired response to COVID-19 vaccination is of particular concern in immunosuppressed patients. To determine the best vaccination strategy for this vulnerable group we performed a single center, 1:1 randomized blinded clinical trial. Patients who failed to seroconvert upon two mRNA vaccinations (BNT162b2 or mRNA-1273) are randomized to receive either a third dose of the same mRNA or the vector vaccine ChAdOx1 nCoV-19.

National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic disease modifying antirheumatic drugs (DMARDs).

This publication provides a thorough analysis of the most relevant topics concerning the management of latent tuberculosis when using biologic and targeted synthetic Disease Modifying Antirheumatic Drugs (DMARDs) by a multidisciplinary, select committee of Austrian physicians. The committee includes members of the Austrian Societies for Rheumatology and Rehabilitation, Pulmonology, Infectiology, Dermatology and Gastroenterology. Consensus was reached on issues regarding screening and treatment of latent tuberculosis and includes separate recommendations for each biologic and targeted synthetic DMARD.

Immunogenicity and safety of a fourth COVID-19 vaccination in rituximab-treated patients: an open-label extension study.

Objectives: Patients under rituximab therapy are at high risk for a severe COVID-19 disease course. Humoral immune responses to SARS-CoV-2 vaccination are vastly diminished in B-cell-depleted patients, even after a third vaccine dose. However, it remains unclear whether these patients benefit from a fourth vaccination and whether continued rituximab therapy affects antibody development.

Neuropsychiatric Systemic Lupus Erythematosus: A Remaining Challenge.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease, which affects a wide range of organs with variable clinical features. Involvement of the nervous system is a challenging and multifaceted manifestation of the disease, presenting with a broad range of symptoms. Neuropsychiatric lupus (NPSLE) encompasses seven syndromes of the peripheral and 12 of the central nervous system, associated with a high disease burden.