Will Peptides Help to Stop COVID-19?

Peptides are widely used for the diagnostics, prevention, and therapy of certain human diseases. How useful can they be for the disease caused by the SARS-CoV-2 coronavirus? In this review, we discuss the possibility of using synthetic and recombinant peptides and polypeptides for prevention of COVID-19 via blocking the interaction between the virus and its main receptor ACE2, as well as components of antiviral vaccines, in particular, against new emerging virus variants.

After JAK inhibitor failure: to cycle or to switch, that is the question - data from the JAK-pot collaboration of registries.

Objectives: The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi.

Methods: This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration).

Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.

Selective differentiation of CD4+ T helper (Th) cells into specialized subsets such as Th1 and Th2 cells is a key element of the adaptive immune system driving appropriate immune responses. Besides those canonical Th-cell lineages, hybrid phenotypes such as Th1/2 cells arise , and their generation could be reproduced . While master-regulator transcription factors like T-bet for Th1 and GATA-3 for Th2 cells drive and maintain differentiation into the canonical lineages, the transcriptional architecture of hybrid phenotypes is less well understood.

Unique and common TCR repertoire features of Ni -, Co -, and Pd -specific human CD154 + CD4+ T cells.

Background: Apart from Ni , Co , and Pd ions commonly trigger T cell-mediated allergic contact dermatitis. However, in vitro frequencies of metal-specific T cells and the mechanisms of antigen recognition remain unclear.

Methods: Here, we utilized a CD154 upregulation assay to quantify Ni -, Co -, and Pd -specific CD4+ T cells in peripheral blood mononuclear cells (PBMC).

The Sensitivity to Change of the ASAS Health Index in an Observational Real-Life Cohort Study.

Objective: The Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health.

Methods: Patients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included.

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration.

Background: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers.

Methods: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included.

PRI: Re-Analysis of a Public Mass Cytometry Dataset Reveals Patterns of Effective Tumor Treatments.

Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm "pattern recognition of immune cells (PRI)" to tackle these high-dimensional protein combinations in the data.

Menstrual blood-derived mesenchymal stromal cells efficiently ameliorate experimental autoimmune encephalomyelitis by inhibiting T cell activation in mice.

Background: Immunosuppressive properties grant mesenchymal stromal cells (MSCs) promising potential for treating autoimmune diseases. As autologous MSCs suffer from limited availability, the readily available allogeneic MSCs isolated from menstrual blood (MB-MSCs) donated by young, healthy individuals offer great potential. Here, we evaluate the therapeutic potential of MB-MSCs as ready-to-use allo-MSCs in multiple sclerosis, an autoimmune disease developed by the activation of myelin sheath-reactive Th1 and Th17 cells, by application in its animal model experimental autoimmune encephalomyelitis (EAE).

TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability.

Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive.

Dysfunction of S100A4 effector memory CD8 T cells aggravates asthma.

Progressive loss of effector functions, especially IFN-γ secreting capability, in effector memory CD8 T (CD8 T ) cells plays a crucial role in asthma worsening. However, the mechanisms of CD8 T cell dysfunction remain elusive. Here, we report that S100A4 drives CD8 T cell dysfunction, impairing their protective memory response and promoting asthma worsening in an ovalbumin (OVA)-induced asthmatic murine model.

Frequencies and TCR Repertoires of Human 2,4,6-Trinitrobenzenesulfonic Acid-specific T Cells.

Allergic contact dermatitis is a widespread T cell-mediated inflammatory skin disease, but monitoring of chemical-specific T cells remains challenging. We here introduce short-term CD154/CD137 upregulation to monitor human T cell responses to the experimental sensitizer 2,4,6-trinitrobenzenesulfonic acid (TNBS). Peripheral blood mononuclear cells (PBMC) from healthy donor buffy coats were TNBS-modified and incubated with unmodified PBMC.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

Aim: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.

Methods: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death.

A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4 T cells and is defective in Crohn´s disease patients.

Immunosuppressive Interleukin (IL)-10 production by pro-inflammatory CD4 T cells is a central self-regulatory function to limit aberrant inflammation. Still, the molecular mediators controlling IL-10 expression in human CD4 T cells are largely undefined. Here, we identify a Notch/STAT3 signaling-module as a universal molecular switch to induce IL-10 expression across human naïve and major effector CD4 T cell subsets.

Mobile Responsive App-A Useful Additional Tool for Data Collection in the German Pregnancy Register Rhekiss?

The German pregnancy register Rhekiss is designed as a nationwide, web-based longitudinal observational cohort established in 2015. The register follows women with inflammatory rheumatic disease prospectively from child wish or early pregnancy until 2 years post-partum. Information on clinical and laboratory parameters, drug treatment, and (adverse) pregnancy outcomes are documented in pre-specified intervals.

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

Objectives: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD).

Methods: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections.

B- and Plasma Cell Subsets in Autoimmune Diseases: Translational Perspectives.

B lymphocytes play a central role in immunity owing to their unique antibody-producing capacity that provides protection against certain infections and during vaccination. In autoimmune diseases, B cells can gain pathogenic relevance through autoantibody production, antigen presentation, and proinflammatory cytokine secretion. Recent data indicate that B and plasma cells can function as regulators through the production of immunoregulatory cytokines and/or employing checkpoint molecules.

An in vitro platform supports generation of human innate lymphoid cells from CD34 hematopoietic progenitors that recapitulate ex vivo identity.

Innate lymphoid cells (ILCs) are critical effectors of innate immunity and inflammation, whose development and activation pathways make for attractive therapeutic targets. However, human ILC generation has not been systematically explored, and previous in vitro investigations relied on the analysis of few markers or cytokines, which are suboptimal to assign lineage identity. Here, we developed a platform that reliably generated human ILC lineages from CD34 hematopoietic progenitors derived from cord blood and bone marrow.

Mast Cells Modulate Antigen-Specific CD8 T Cell Activation During LCMV Infection.

Mast cells (MCs), strategically localized at mucosal surfaces, provide first-line defense against pathogens and shape innate and adaptive immune responses. Recent studies have shown that MCs are involved in pathogenic responses to several viruses including herpes simplex viruses, dengue virus, vaccinia virus and influenza virus. However, the underlying mechanisms of MCs in the activation of CD8 T cells during viral infections are not fully understood.

Interplay Between Microbiota, Toll-Like Receptors and Cytokines for the Maintenance of Epithelial Barrier Integrity.

The intestinal tract is densely populated by microbiota consisting of various commensal microorganisms that are instrumental for the healthy state of the living organism. Such commensals generate various molecules that can be recognized by the Toll-like receptors of the immune system leading to the inflammation marked by strong upregulation of various proinflammatory cytokines, such as TNF, IL-6, and IL-1β. To prevent excessive inflammation, a single layer of constantly renewing, highly proliferating epithelial cells (IEC) provides proper segregation of such microorganisms from the body cavities.

Evidence for tmTNF reverse signaling : Implications for an arginase-1-mediated therapeutic effect of TNF inhibitors during inflammation.

In order to ascertain the significance of transmembrane tumor necrosis factor (tmTNF) reverse signaling , we generated a triple transgenic mouse model (3TG, TNFR1-/-, TNFR2-/-, and tmTNFKI/KI) in which all canonical tumor necrosis factor (TNF) signaling was abolished. In bone-marrow-derived macrophages harvested from these mice, various anti-TNF biologics induced the expression of genes characteristic of alternative macrophages and also inhibited the expression of pro-inflammatory cytokines mainly through the upregulation of arginase-1. Injections of TNF inhibitors during arthritis increased pro-resolutive markers in bone marrow precursors and joint cells leading to a decrease in arthritis score.