Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice.

Introduction: Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA).

NHC-gold compounds mediate immune suppression through induction of AHR-TGFβ1 signalling in vitro and in scurfy mice.

Gold compounds have a long history of use as immunosuppressants, but their precise mechanism of action is not completely understood. Using our recently developed liver-on-a-chip platform we now show that gold compounds containing planar -heterocyclic carbene (NHC) ligands are potent ligands for the aryl hydrocarbon receptor (AHR). Further studies showed that the lead compound (MC3) activates TGFβ1 signaling and suppresses CD4 T-cell activation in vitro, in human and mouse T cells.

Scurfy Mice Develop Features of Connective Tissue Disease Overlap Syndrome and Mixed Connective Tissue Disease in the Absence of Regulatory T Cells.

Due to a missense mutation in the gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies have outlined the systemic inflammatory disease and demonstrated production of anti-nuclear antibodies (ANA) in scurfy mice.

Regulatory T-cell deficiency leads to pathogenic bullous pemphigoid antigen 230 autoantibody and autoimmune bullous disease.

Background: Autoimmune bullous diseases/dermatoses (AIBDs) are severe autoantibody-mediated skin diseases. The pathogenic relevance of autoreactive CD4 T cells for the induction of autoantibody production remains to be fully evaluated. Scurfy mice lack functional regulatory T (Treg) cells, experience spontaneous activation of autoreactive CD4 T cells, and display severe erosive skin lesions suggestive of AIBDs.

Regulatory T cell deficient scurfy mice exhibit a Th2/M2-like inflammatory response in the skin.

Background: Scurfy mice have a functional defect in regulatory T cells (Treg), which leads to lethal multi-organ inflammation. The missing Treg function results in uncontrolled autoimmune cellular and humoral inflammatory responses. We and others have previously shown that during the course of disease scurfy mice develop severe skin inflammation and autoantibodies including anti-nuclear autoantibodies (ANA).

Routine Laboratory Parameter Dynamics and Laboratory Adverse Events in Psoriasis Patients on Long-term Treatment with Adalimumab, Etanercept, and Ustekinumab.

Only limited data on laboratory parameter dynamics and safety under prolonged biologic treatment in a "real-world" scenario are available for recommendations on screening and monitoring. This study is a retrospective analysis of routine parameter dynamics and laboratory adverse events (LAE) in psoriasis patients on long-term treatment (n = 199) with tumour necrosis factor (TNF)-α-antagonists (adalimumab, etanercept), and the interleukin (IL)12/23-antagonist ustekinumab. Overall, neutrophil (PMN) counts (-11%) and triglycerides (+9%) changed considerably.

Interindividual variation of NETosis in healthy donors: introduction and application of a refined method for extracellular trap quantification.

Neutrophil extracellular trap (NET) formation is a mechanism of innate immune defence by which neutrophil (polymorphonuclear) granulocytes (PMN) produce net-like structures of decondensed chromatin decorated with antimicrobial peptides for trapping and possibly killing microorganisms. If this process leads to cell death, it is termed NETosis. Alterations of this particular mechanism have been reported to be involved in the pathogenesis of chronic inflammatory diseases including psoriasis and lupus erythematosus.

Correlation of autoantibodies against BP180/BP230 in response to topical corticosteroids in patients with bullous pemphigoid.

Topical steroids are effective in treating bullous pemphigoid (BP). Autoantibodies against BP180 are related to disease activity, but correlation of these autoantibodies with response to topical steroid therapy has not yet been clearly evaluated. We investigate the usefulness of close and early monitoring of autoantibodies against BP180 and BP230 for assessment of response to therapy and early detection of therapeutic failure in BP patients treated topically.

Altered expression of keratin 14 in lesional epidermis of autoimmune skin diseases.

Background: Keratin 14 (K14) is an intermediate filament protein that is mainly expressed in the basal layer of healthy stratified epithelia. K14 has been identified as an autoantigen in the autoimmune-mediated skin disease of Scurfy mice and patients with the "immune dysregulation polyendocrinopathy, enteropathy, and X-linked" syndrome.

Objectives: To examine whether K14 is a target protein in autoimmune skin diseases (ASD), we analyzed the expression pattern of K14 in lesional skin of patients with lichen ruber, cutaneous lupus erythematosus, dermatomyositis, graft-versus-host disease, psoriasis, and pemphigus vulgaris, and evaluated the reactivity of patient sera with recombinantly expressed and epidermis-derived K14.

TGF-β1-induced regulatory T cells.

Besides central tolerance peripheral tolerance is an important mechanism to avoid development of autoimmunity. Naturally occurring thymic-derived regulatory T cells (nTreg) mediate peripheral tolerance by suppressing autoreactive T cells clones having escaped thymic deletional control. This implies that nTreg have therapeutic potential to dampen autoimmune disease.

Regulatory T cell-deficient scurfy mice develop systemic autoimmune features resembling lupus-like disease.

Introduction: Scurfy mice are deficient in regulatory T cells (Tregs), develop a severe, generalized autoimmune disorder that can affect almost every organ and die at an early age. Some of these manifestations resemble those found in systemic lupus erythematosus (SLE). In addition, active SLE is associated with low Treg numbers and reduced Treg function, but direct evidence for a central role of Treg malfunction in the pathophysiology of lupus-like manifestations is still missing.

Baseline anti-dsDNA concentrations and previous treatments predict response to Adalimumab and Etanercept: a retrospective investigation of 146 psoriasis patients.

Background: Adalimumab and Etanercept are TNF-α antagonists commonly used for treatment of moderate-to-severe psoriasis and psoriatic-arthritis. Reliable instruments to assist the selection of patients for a specific treatment in a real-world scenario are unavailable.

Objective: To identify patient characteristics and baseline laboratory parameters predicting response to Adalimumab- and Etanercept-treatment.

Analysis of high-dose intravenous immunoglobulin therapy in 16 patients with refractory autoimmune blistering skin disease: high efficacy and no serious adverse events.

High-dose intravenous immunoglobulin (IVIG) therapy is used in patients with severe autoimmune blistering diseases that are refractory to standard immunosuppressive therapy. To determine the efficacy and frequency of adverse events of IVIG therapy, we retrospectively analysed data for 16 patients with pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, bullous pemphigoid and paraneoplastic bullous pemphigoid. Frequency of adverse reactions and efficacy of IVIG were analysed over time with a scoring system for every 6 months of IVIG therapy.