A5001463705- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Phosphodiesterase function and regulation
- Chronic Lymphocytic Leukemia Research
- Vasculitis and related conditions
- Sexual function and dysfunction studies
- Pharmacological Effects and Toxicity Studies
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Cell Adhesion Molecules Research
- Diabetes and associated disorders
- Eosinophilic Disorders and Syndromes
- COVID-19 Clinical Research Studies
- Autoimmune and Inflammatory Disorders Research
- Rheumatoid Arthritis Research and Therapies
- Immune responses and vaccinations
- Systemic Lupus Erythematosus Research
- Cell death mechanisms and regulation
- Spondyloarthritis Studies and Treatments
- Blood disorders and treatments
- Pharmaceutical studies and practices
- Psoriasis: Treatment and Pathogenesis
- Bioactive Natural Diterpenoids Research
- Otitis Media and Relapsing Polychondritis
University Medical Center Freiburg
2015-2024
University of Freiburg
2016-2024
Medical University of Graz
2024
Center for Rheumatology
2018-2020
Universidade Estadual de Campinas (UNICAMP)
2007-2016
Centre for Chronic Disease Control
2016
B cell depletion with rituximab (RTX) is approved for treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitides (AAV). Recently, RTX has been shown to be effective in AAV maintenance therapy, but an optimal schedule unknown the time repopulation after not studied.Retrospective single-center analysis patients AAV, RA or connective tissue disease (CTD) treated RTX.Beginning within first year was observed 93% 88% CTD patients. Only 10% granulomatosis polyangiitis (GPA) microscopic...
Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) approved for the treatment of rheumatoid arthritis (RA) its mechanism action attributed to effects T-cells. It known that modulates expression ligands CD80 CD86 antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 function as APC, we hypothesize are a direct target...
Defective FAS (CD95/Apo-1/TNFRSF6) signaling causes autoimmune lymphoproliferative syndrome (ALPS). Hypergammaglobulinemia is a common feature in ALPS with mutations (ALPS-FAS), but paradoxically, fewer conventional memory cells differentiate from FAS-expressing germinal center (GC) B cells. Resistance to FAS-induced apoptosis does not explain this phenotype. We tested the hypothesis that defective non-apoptotic may contribute impaired cell differentiation ALPS. analyzed secondary lymphoid...
B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral development to identify the causes for defect reconstitution RTX therapy.
The COVID-19 course and immunity differ in children adults. We analyzed immune response dynamics 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial is plasmablast-driven children. Four infection, show an enhanced specific antibody lower but detectable spike 1 protein (S1)-specific B T cell responses than their parents. While antibodies decline, neutralizing activity breadth increase both groups. frequencies of S1-specific remain stable. However,...
The 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, sildenafil, is a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor used for penile erectile dysfunction. In the search more potent and selective PDE5 inhibitors, new sildenafil analogues (6a−v), characterized by presence on sulfonyl group in 5′ position of novel N-4-substituted piperazines or ethylenediamine moiety, were prepared traditional microwave-assisted synthesis...
Abstract TNF receptor superfamily members (TNFRSF) such as CD40, Fas and TRAIL 2 (TRAILR2) participate to the adaptive immune response by eliciting survival, proliferation, differentiation and/or cell death signals. The balance between these signals determines fate of response. It was previously reported that receptors are able self-assemble in absence ligand through their extracellular regions. However, role this oligomerization is not well understood, none proposed hypotheses take into...
Objectives Axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) may have a profound impact on sleep health-related quality of life. The aim this study was to assess life determine associated factors in patients treated with spondyloarthritides (SpA). Methods Cross-sectional questionnaire-based assessment behaviour, life, functional impairment depression (Regensburg Insomnia Scale, WHO Quality Life questionnaire, Funktionsfragebogen Hannover Beck Depression Inventory II, Patient...
Background Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic are in clinical trials numerous other IMIDs. However, detailed studies investigating effects different JAK on B cells missing. Within this study, we therefore aimed to characterize effect inhibition cell compartment. Methods To end, investigated compartment under compared specific tofacitinib (pan-JAK), baricitinib...
Envenoming by Bothrops jararaca can result in local pain, edema, hemorrhage and necrosis, partially mediated snake venom metalloproteinases (SVMPs). Here, we describe the characterization of BJ-PI2, a P-I class SVMP from B. venom, its tissue actions.BJ-PI2 was purified combination gel filtration, anion-exchange chromatography reverse phase HPLC, identified mass spectrometry. Clotting fibrin(ogen)olytic activities were assayed using conventional methods. Hemorrhagic activity changes vascular...
The maintenance of B cell homeostasis requires a tight control generation, survival, activation, and maturation. In lymphocytes upon increased sensitivity to apoptotic signals helps controlling differentiation proliferation. death receptor Fas is important in this context because genetic mutations humans lead an autoimmune lymphoproliferative syndrome that similar lymphoproliferation observed Fas-deficient mice. contrast, the physiological role TNF-related apoptosis-inducing ligand receptors...
CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies HIV-infected children and adolescents receiving ART, their association with risk factors. DESIGN SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 (54.6% male; median age 7.48 years) were analyzed, mean 2.6...
BackgroundNitrergic nerves and endothelial cells release nitric oxide (NO) in the corpus cavernosum (CC), a key mediator that stimulates soluble guanylyl cyclase to increase cGMP levels cause penile erection.Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong NO effects by inhibiting breakdown.
Respiratory tract infections (RTIs) are the most common in patients with rheumatic diseases under immunosuppressive treatment and may contribute to morbidity mortality as well increased healthcare costs. However, date only limited data on infection risk spondyloarthritis (SpA) available. In this study we assessed occurrence of respiratory a monocentric real-world cohort consisting 330 (168 psoriatic arthritis 162 axial patients) determined factors associated risk. Out SpA patients, 89.3% had...
Primary antiphospholipid syndrome (PAPS) is a life-threatening clotting disorder mediated by pathogenic autoantibodies. Here we dissect the origin of self-reactive B cells in human PAPS using peripheral blood and bone marrow patients with triple-positive via combined single-cell RNA sequencing, cell receptors (BCR) repertoire profiling, CITEseq analysis single immortalization. We find that (aPL)-specific are present naive compartment, polyreactive, derived from natural repertoire....
Meeting abstractAutoimmune lymphoproliferative syndrome (ALPS) is characterized by disease, autoimmune cytopenias and increased susceptibility to lymphoid malignancies. Central the pathophysiology of disease are defects in FAS signaling leading impaired lymphocyte homeostasis. Most patients harbor heterozygous germline or somatic mutations FAS. The hallmark FAS-mediated apoptosis activated T cells presence atypical "double-negative" (CD3+TCRalpha/beta+CD4-CD8-). While essential for deletion...
<h3>Background</h3> B cells are pivotal to the pathogenesis of many autoimmune diseases including rheumatoid arthritis (RA). Tofacitinib, a JAK inhibitor, is effective and safe in treatment RA. Tofacitinib interferes with signal transduction via cytokine receptors using common γ-chain. <h3>Objectives</h3> Despite extensive data on T lymphocytes, impact tofacitinib lymphocytes poorly understood. In this study we assess effect differentiation naive B-lymphocytes their function....