Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis.

Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases.

Circulating CD4+CD8+ double-positive T-cells display features of innate and adaptive immune function in granulomatosis with polyangiitis.

Objectives: To examine functional features of CD4+CD8+ double-positive T-cells in patients with granulomatosis with polyangiitis (GPA) using phenotypic and transcriptomic analysis.

Methods: Staining of cellular surface marker was performed using freshly collected whole blood. For intracellular cytokine staining freshly collected whole blood was stimulated with phorbol myristate acetate and ionomycin.

Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV.

[Granulomatosis with polyangiitis].

Granulomatosis with polyangiitis (GPA) is a potentially life-threatening, rare disease. The etiology is unknown. GPA is histomorphologically characterized by extravascular necrotizing granulomatous inflammation and a systemic necrotizing vasculitis of small to medium-sized vessels.

Environmental factor and inflammation-driven alteration of the total peripheral T-cell compartment in granulomatosis with polyangiitis.

Autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. Autoantibody production and an imbalance of effector and regulatory T-cells are hallmarks of autoimmune dysregulation. While expansion of circulating effector memory T-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral T-cell compartment have remained poorly understood so far.

[Effector memory T‑cells in the pathogenesis of ANCA-associated vasculitides. German version].

Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory T‑cells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including T‑helper type 1 (Th1) CD4+ T‑cells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory T‑cells is skewed towards an increase of Th2 type, Th17 and Th22 cell fractions in GPA.

Effector memory T‑cells in the pathogenesis of ANCA-associated vasculitides.

Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory T‑cells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including T‑helper type 1 (Th1) CD4 T‑cells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory T‑cells is skewed towards an increase of Th2 type, Th17, and Th22 cell fractions in GPA.

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines.

Frontotemporal dementia mimicking bipolar disorder.

Frontotemporal dementia is a cause of behavioral disturbance that usually appears in individuals between 45 and 65 years of age. The authors present the case of a 65-year-old patient that illustrates how frontotemporal dementia can be misdiagnosed based on a behavioral pattern that suggests the presence of a primary mood disorder. Early accurate diagnosis of frontotemporal dementia and subsequent supportive measures can allow patients and families to make important decisions about business and legal affairs and how to spend remaining leisure time in the most meaningful and enjoyable way possible.

Fronts in randomly advected and heterogeneous media and nonuniversality of Burgers turbulence: theory and numerics.

A recently established mathematical equivalence-between weakly perturbed Huygens fronts (e.g., flames in weak turbulence or geometrical-optics wave fronts in slightly nonuniform media) and the inviscid limit of white-noise-driven Burgers turbulence-motivates theoretical and numerical estimates of Burgers-turbulence properties for specific types of white-in-time forcing.

Clustering of randomly advected low-inertia particles: a solvable model.

Measurements and simulations indicate that the particle-pair radial distribution function in isotropic turbulence is a power law in a range of length scales below the Kolmogorov scale for Stokes number St<<1. In this range, the exponent is proportional to St1St2 for unlike particles (1 and 2) in a bidispersion, hence St2 for a monodispersion. Here, this result is derived from a model of particle response to random advection.

Prandtl-number dependence of turbulent flame propagation.

Inertial-range cascade phenomenology is used to predict Prandtl-number (Pr) dependencies of turbulent flame properties. A unified picture of turbulent flame structure and burning velocity is developed that encompasses all Pr regimes. Implications of the analysis for gaseous flames (Pr near unity), autocatalytic fronts in liquids (high Pr), and astrophysical flames (low Pr) are noted.

Kinematics of small scale anisotropy in turbulence.

A simple, empirically motivated model is proposed to explain the transfer of imposed large scale anisotropy to small scales in high-Reynolds-number turbulence. Observed power-law scalings of anisotropy metrics are interpreted as manifestations of power-law scalings governing high-gradient regions resulting from compressional eddy motions. The model is used to interpret the measured moment-order dependencies of the exponents and amplitudes of odd-order structure functions and derivative moments that vanish in the absence of anisotropy.