Metabolomic signature identifies HDL and apolipoproteins as potential biomarker for systemic sclerosis with interstitial lung disease.

Background: High-density lipoproteins (HDL) affect endothelial functions such as the expression of endothelial cell adhesion molecules and exert anti-apoptotic/-thrombotic functionalities. Therefore, profound analysis of lipoproteins may unveil biomarkers for (micro-)vasculopathy in systemic sclerosis (SSc) and mortality determining disease manifestations like interstitial lung disease (SSc-ILD). Because nuclear magnetic resonance (NMR) spectroscopy provides a wide range of lipoprotein parameters beyond the capabilities of classical analyses it has been used herein to examine lipoprotein profiles in SSc.

Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases.

Background: Chronic inflammatory diseases (CIDs) are systems disorders that affect diverse organs including the intestine, joints and skin. The essential amino acid tryptophan (Trp) can be broken down to various bioactive derivatives important for immune regulation. Increased Trp catabolism has been observed in some CIDs, so we aimed to characterise the specificity and extent of Trp degradation as a systems phenomenon across CIDs.

Detecting and exploiting the circadian clock in rheumatoid arthritis.

Over the past four decades, research on 24-h rhythms has yielded numerous remarkable findings, revealing their genetic, molecular, and physiological significance for immunity and various diseases. Thus, circadian rhythms are of fundamental importance to mammals, as their disruption and misalignment have been associated with many diseases and the abnormal functioning of many physiological processes. In this article, we provide a brief overview of the molecular regulation of 24-h rhythms, their importance for immunity, the deleterious effects of misalignment, the link between such pathological rhythms and rheumatoid arthritis (RA), and the potential exploitation of chronobiological rhythms for the chronotherapy of inflammatory autoimmune diseases, using RA as an example.

The Lübeck Medication Satisfaction Questionnaire-A Novel Measurement Tool for Therapy Satisfaction.

Background: Therapy satisfaction is widely considered an important aspect of clinical care. Still, there are currently no freely available questionnaires for its measurement. We developed the Lübeck Medication Satisfaction Questionnaire (LMSQ) for that purpose.

Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium.

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022.

Potential effects of shift work on skin autoimmune diseases.

Shift work is associated with systemic chronic inflammation, impaired host and tumor defense and dysregulated immune responses to harmless antigens such as allergens or auto-antigens. Thus, shift workers are at higher risk to develop a systemic autoimmune disease and circadian disruption with sleep impairment seem to be the key underlying mechanisms. Presumably, disturbances of the sleep-wake cycle also drive skin-specific autoimmune diseases, but epidemiological and experimental evidence so far is scarce.

Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19.

https://bit.ly/3pqM9Vv.

Autoimmune pre-disease.

Approximately 5% of the world-wide population is affected by autoimmune diseases. Overall, autoimmune diseases are still difficult to treat, impose a high burden on patients, and have a significant economic impact. Like other complex diseases, e.

Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms.

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases.

An estimated 20-25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors.

Induced antibodies directed to the angiotensin receptor type 1 provoke skin and lung inflammation, dermal fibrosis and act species overarching.

Objective: To determine contributions and functions of autoantibodies (Abs) directed to the angiotensin receptor type 1 (AT1R), which are suggested to be involved in the pathogenesis of AT1R Abs-related diseases such as systemic sclerosis (SSc).

Methods: C57BL/6J mice were immunised with membrane-embedded human AT1R or empty membrane as control. Mice deficient for CD4 or CD8 T cells and B cells were immunised with membrane-embedded AT1R or an AT1R peptide proposed to be a dominant T cell epitope.

The contribution of sleep to the neuroendocrine regulation of rhythms in human leukocyte traffic.

Twenty-four-hour rhythms in immune parameters and functions are robustly observed phenomena in biomedicine. Here, we summarize the important role of sleep and associated parameters on the neuroendocrine regulation of rhythmic immune cell traffic to different compartments, with a focus on human leukocyte subsets. Blood counts of "stress leukocytes" such as neutrophils, natural killer cells, and highly differentiated cytotoxic T cells present a rhythm with a daytime peak.

Short regulatory DNA sequences to target brain endothelial cells for gene therapy.

Gene vectors targeting CNS endothelial cells allow to manipulate the blood-brain barrier and to correct genetic defects in the CNS. Because vectors based on the adeno-associated virus (AAV) have a limited capacity, it is essential that the DNA sequence controlling gene expression is short. In addition, it must be specific for endothelial cells to avoid off-target effects.

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases.

Regulatory T cells (Treg) are crucial for the maintenance of peripheral tolerance and for the control of ongoing inflammation and autoimmunity. The cytokine interleukin-2 (IL-2) is essentially required for the growth and survival of Treg in the peripheral lymphatic tissues and thus plays a vital role in the biology of Treg. Most autoimmune and rheumatic diseases exhibit disturbances in Treg biology either at a numerical or functional level resulting in an imbalance between protective and pathogenic immune cells.

Brain endothelial specific gene therapy improves experimental Sandhoff disease.

In Tay-Sachs and Sandhoff disease, a deficiency of the lysosomal enzyme β-hexosaminidase causes GM2 and other gangliosides to accumulate in neurons and triggers neurodegeneration. Although the pathology centers on neurons, β-hexosaminidase is mainly expressed outside of neurons, suggesting that gene therapy of these diseases should target non-neuronal cells to reconstitute physiological conditions. Here, we tested in mice, a model of Sandhoff disease, to determine whether endothelial expression of the genes for human β-hexosaminidase subunit A and B (, ) is able to reduce disease symptoms and prolong survival of the affected mice.

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

Objective: Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits.