Adult-Onset Still's Disease: Clinical Aspects and Therapeutic Approach.

Adult-onset Still's disease (AoSD) is a rare systemic autoinflammatory disease characterized by arthritis, spiking fever, skin rash and elevated ferritin levels. The reason behind the nomenclature of this condition is that AoSD shares certain symptoms with Still's disease in children, currently named systemic-onset juvenile idiopathic arthritis. Immune dysregulation plays a central role in AoSD and is characterized by pathogenic involvement of both arms of the immune system.

Mitigated viral myocarditis in A/J mice by the immunoproteasome inhibitor ONX 0914 depends on inhibition of systemic inflammatory responses in CoxsackievirusB3 infection.

A preclinical model of troponin I-induced myocarditis (AM) revealed a prominent role of the immunoproteasome (ip), the main immune cell-resident proteasome isoform, in heart-directed autoimmunity. Viral infection of the heart is a known trigger of cardiac autoimmunity, with the ip enhancing systemic inflammatory responses after infection with a cardiotropic coxsackievirusB3 (CV). Here, we used ip-deficient A/J-LMP7 mice to investigate the role of ip-mediated effects on adaptive immunity in CV-triggered myocarditis and found no alteration of the inflammatory heart tissue damage or cardiac function in comparison to wild-type controls.

Correction to: Osteoporosis in patients with rheumatoid arthritis: trends in the German National Database 2007-2017.

The original article can be found online.

Factors associated with treatment satisfaction in patients with rheumatoid arthritis: data from the biological register RABBIT.

Objective: To assess satisfaction with the effectiveness and tolerability of treatments in patients with rheumatoid arthritis (RA).

Methods: Patients from the RABBIT register, starting a biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drug (DMARD), or a conventional synthetic (cs)DMARD treatment after ≥1 csDMARD failure, were included. Treatment satisfaction was measured after 1 year of treatment in four categories and binarised for analysis.

In Situ Maturation and Tissue Adaptation of Type 2 Innate Lymphoid Cell Progenitors.

Innate lymphoid cells (ILCs) are generated early during ontogeny and persist predominantly as tissue-resident cells. Here, we examined how ILCs are maintained and renewed within tissues. We generated a single cell atlas of lung ILC2s and found that Il18r1 ILCs comprise circulating and tissue-resident ILC progenitors (ILCP) and effector-cells with heterogeneous expression of the transcription factors Tcf7 and Zbtb16, and CD103.

Profiling of IgG antibodies targeting unmodified and corresponding citrullinated autoantigens in a multicenter national cohort of early arthritis in Germany.

Objective: To assess the diagnostic potential of IgG antibodies to citrullinated and corresponding native autoantigens in early arthritis.

Methods: IgG autoantibodies to 390 distinct unmodified and corresponding in vitro citrullinated recombinant proteins were measured by a multiplex assay in baseline blood samples from a German multicenter national cohort of 411 early arthritis patients (56.5 ± 14.

Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception.

Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)".

Osteoporosis in patients with rheumatoid arthritis: trends in the German National Database 2007-2017.

Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years.

Level of Tumor Necrosis Factor Production by Stimulated Blood Mononuclear Cells Can Be Used to Predict Response of Patients With Inflammatory Bowel Diseases to Infliximab.

Background & Aims: A substantial proportion patients with inflammatory bowel disease (IBD) have a primary non-response to infliximab; markers are needed to identify patients most likely to respond to treatment. We investigated whether production of tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMCs) can be used as a marker to predict response.

Methods: We performed a prospective study of 41 adults with IBD (mean age, 38 years; 21 male; 21 with Crohn's disease and 20 with ulcerative colitis) not treated with a biologic agent within the past 6 months; patients were given their first infusion of infliximab at a hospital or clinic in Berlin, Germany.

c-FLIP is crucial for IL-7/IL-15-dependent NKp46 ILC development and protection from intestinal inflammation in mice.

NKp46 innate lymphoid cells (ILC) modulate tissue homeostasis and anti-microbial immune responses. ILC development and function are regulated by cytokines such as Interleukin (IL)-7 and IL-15. However, the ILC-intrinsic pathways translating cytokine signals into developmental programs are largely unknown.

is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling.

The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets.

Effects of myeloid cell-restricted TNF inhibitors in vitro and in vivo.

Systemic TNF neutralization can be used as a therapy for several autoimmune diseases. To evaluate the effects of cell type-restricted TNF blockade, we previously generated bispecific antibodies that can limit TNF secretion by myeloid cells (myeloid cell-specific TNF inhibitors or MYSTIs). In this study several such variable domain (VH) of a camelid heavy-chain only antibody-based TNF inhibitors were compared in relevant experimental models, both in vitro and in vivo.

Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Studies in rodent models demonstrated an association of CNS-infiltrating monocyte-derived macrophages with disease severity. However, little is known about humans.

Modulation of bioavailability of proinflammatory cytokines produced by myeloid cells.

In spite of successful therapeutic neutralization of proinflammatory cytokines in several autoimmune diseases, such therapy is not entirely free of side effects. The main reason relates to the fact that cytokine signaling may have protective components that need to be spared. Several approaches to achieve a less damaging cytokine inhibition are being explored.

The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation.

Innate lymphoid cells (ILCs) are tissue resident cells with organ-specific properties. Here, we show that the central nervous system (CNS) encompasses ILCs. In particular, CD3NK1.

IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis.

An acquired deficiency of interleukin-2 (IL-2) and related disturbances in regulatory T cell (Treg) homeostasis play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Low-dose IL-2 therapy was shown to restore Treg homeostasis in patients with active SLE and its clinical efficacy is currently evaluated in clinical trials. Lupus nephritis (LN), a challenging organ manifestation in SLE, is characterized by the infiltration of pathogenic CD4+ T cells into the inflamed kidney.

Memory CD8 T Cell Protection From Viral Reinfection Depends on Interleukin-33 Alarmin Signals.

Memory CD8 cytotoxic T lymphocytes (CTLs) can protect against viral reinfection. However, the signals driving rapid memory CTL reactivation have remained ill-defined. Viral infections can trigger the release of the alarmin interleukin-33 (IL-33) from non-hematopoietic cells.

Recruitment of Histone Methyltransferase Ehmt1 to Foxp3 TSDR Counteracts Differentiation of Induced Regulatory T Cells.

Differentiation toward CD4 regulatory T (Treg) cells is essentially dependent on an epigenetic program at Treg signature genes, which involves remodeling of the Treg-specific demethylated regions (TSDRs). In particular, the epigenetic status of the conserved non-coding sequence 2 of Foxp3 (Foxp3 TSDR) determines expression stability of the master transcription factor and thus Treg lineage identity. However, the molecular mechanisms controlling the epigenetic remodeling at TSDRs in Treg and conventional T cells are largely unknown.

Novel paradigms in systemic lupus erythematosus.

The heterogeneity of systemic lupus erythematosus (SLE), long recognised by clinicians, is now challenging the entire lupus community, from geneticists to clinical investigators. Although the outlook for patients with SLE has greatly improved, many unmet needs remain, chief of which is the development of safer and more efficacious therapies. To develop innovative therapies, a far better understanding of SLE pathogenesis as it relates to the array of clinical phenotypes is needed.

Surface Barcoding of Live PBMC for Multiplexed Mass Cytometry.

Sample barcoding is a powerful method for harmonizing mass cytometry data. By assigning a unique combination of barcode labels to each cell sample, a set of individual samples can be pooled and further processed and acquired as a large, single sample. For assays that require uncompromised profiling of cell-surface markers on live cells, barcoding by metal-labeled antibodies targeting cell-surface epitopes is the barcoding approach of choice.

IL-10-producing B cells are characterized by a specific methylation signature.

Among the family of regulatory B cells, the subset able to produce interleukin-10 (IL-10) is the most studied, yet its biology is still a matter of investigation. The DNA methylation profiling of the il-10 gene locus revealed a novel epigenetic signature characterizing murine B cells ready to respond through IL-10 synthesis: a demethylated region located 4.5 kb from the transcription starting site (TSS), that we named early IL10 regulatory region (eIL10rr).