Klaus Tenbrock

Klaus Tenbrock
RWTH Aachen University · Department of Paediatric and Adolescent Medicine

About

211
Publications
20,426
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
7,042
Citations
Citations since 2017
77 Research Items
3858 Citations
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800

Publications

Publications (211)
Article
Full-text available
Background To analyze therapy adherence, safety, and outcome in adult patients with juvenile idiopathic arthritis (JIA) treated with the etanercept biosimilar Benepali ® (Biogen Inc, Cambridge, USA). Methods Data from the prospective registry, JuMBO (Juvenile arthritis MTX/Biologics long-term Observation), were used for the analysis. JuMBO is a lo...
Article
Full-text available
Background: CD4+ T cells critically contribute to the initiation and perturbation of inflammation. When CD4+ T cells enter inflamed tissues, they adapt to hypoxia and oxidative stress conditions, and to a reduction in nutrients. We aimed to investigate how this distinct environment regulates T cell responses within the inflamed joints of patients...
Article
Background New therapeutic strategies for juvenile idiopathic arthritis (JIA) have evolved within the past ten years, and as a result, an update of the 2011 recommendations of the German management guidelines was initiated. Methods A systemic literature review was performed, overarching principles were proposed and pre-selected via an online surve...
Chapter
Der systemische Lupus erythematodes (SLE) ist eine Autoimmunerkrankung, die mit einer Immunkomplex-vermittelten Vaskulitis verschiedener Organe einhergeht. Für die Prognose entscheidend ist die Beteiligung der Nieren und des ZNS. Die Ursachen des SLE sind multifaktoriell: Genetische Suszeptibilität, exogene Einflüsse, wie z. B. Infektionen, humoral...
Article
Background The ProKind Commission of the Society for Paediatric and Adolescent Rheumatology (GKJR) has developed evidence- and consensus-based protocols for the diagnosis and therapy of children and adolescents with defined rheumatic diseases (e.g., [1]). In the ProKind-Rheuma project, it is now investigated whether the protocols are followed in ev...
Preprint
Full-text available
Introduction: Tofactinib is a JAK inhibitor approved for ulcerative colitis in humans. Despite of its’ proven effectiveness in humans, mechanistic data are scarce on the effectiveness of Tofactinib in experimental colitis in mice. Methods: We induced experimental colitis by transfer of CD4 + CD25- isolated T cells into lymphopenic RAG2-/- mice and...
Article
T helper cells aid B cells with the production of antibodies and thus play a central role in disease development of systemic lupus erythematosus (SLE). Numerous T helper cell abnormalities have been described in SLE patients that contribute to disease pathophysiology and provide suitable targets for therapeutic intervention. In addition, T effector...
Article
Zusammenfassung Die Initiative Protokolle in der Kinderrheumatologie (Pro-Kind) der GKJR hat es sich zum Ziel gesetzt, durch Entwicklung von Therapieprotokollen die Behandlung von kindlich-rheumatischen Erkrankungen zu standardisieren und dadurch das Outcome zu verbessern. Seit 2019 wird die Überprüfung der Effektivität dieser standardisierten Prot...
Article
Full-text available
Background To describe treatment practices for juvenile proliferative lupus nephritis (LN) class III and IV of pediatric rheumatologists and nephrologists in Germany and Austria in preparation for a treat-to-target treatment protocol in LN.Methods Survey study by members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German...
Article
Zusammenfassung Schmerzhafte Bewegungseinschränkungen und Gelenkschwellungen, der Nachweis von entzündlichen Veränderungen in der Sonografie oder Kernspintomografie sowie unauffällige laborchemische Untersuchungen sind typische Befunde der juvenilen idiopathischen Arthritis. Allerdings müssen in der differenzialdiagnostischen Abklärung von Arthropa...
Article
Full-text available
Autoimmune diseases are characterized by a failure of tolerance to own body components resulting in tissue damage. Regulatory T cells are gatekeepers of tolerance. This review focusses on the function and pathophysiology of regulatory T cells in the context of autoimmune diseases including rheumatoid and juvenile idiopathic arthritis as well as sys...
Article
Objective Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease of unknown origin. The regulation of inflammatory processes involves multiple cellular steps including mRNA transcription and translation. Different miRNAs tightly control these processes. We aimed to determine the roles of specific miRNAs within JIA pathogenesis. Meth...
Article
The cAMP responsive element modulator (CREM) is a transcriptional regulator of different effector cytokines in CD4 ⁺ T cells including IL-2, IL-17, IL-21 but also IL-4 and IL-13 and thus an important determinant of central T helper cell functions. Our review gives an overview over the regulation of CREM in T cells and the pleiotropic effects of CRE...
Article
Full-text available
Background: Early adversity is believed to alter the body's stress-response systems, putting children at increased risk for somatic and mental health problems. However, it remains unclear whether such alterations normalize under improved caregiving experiences. Thus, the goal of the present study was to investigate (a) whether children in foster c...
Article
Background Various treatment strategies are used for children with newly diagnosed polyarticular JIA. MTX is usually prescribed, sometimes in combination with high-dose intravenous glucocorticoid pulses (HDGC) or multiple intra-articular GC injections (IAGC). These different approaches were considered in the German consensus-based treatment protoco...
Article
Background: Deciphering the function of the many genes previously classified as uncharacterized "open reading frame" (orf) completes our understanding of cell function and its pathophysiology. Methods: Whole-exome sequencing, yeast 2-hybrid and transcriptome analyses together with molecular characterization are used here to uncover the function...
Article
Full-text available
MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic...
Preprint
Full-text available
Background Early adversity is believed to alter the body’s stress response systems, putting children at increased risk for somatic and mental health problems. However, it remains unclear whether such alterations normalize under improved caregiving experiences. Thus, the goal of the present study was to investigate i) whether children in foster care...
Article
Full-text available
Oxidative stress is a major component of cellular damage in T cells from patients with systemic lupus erythematosus (SLE) resulting amongst others in the generation of pathogenic Th17 cells. The NRF2/Keap1 pathway is the most important antioxidant system protecting cells from damage due to oxidative stress. Activation of NRF2 therefore seems to rep...
Article
Full-text available
Background Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with dysregulation of the innate immune system driven by cytokines. A major role is ascribed to interleukin-1β (IL-1β), supporting the autoinflammatory character of the disease and offering an effective blocking mechanism for treatment. Here we present clinical practice d...
Preprint
Full-text available
Background: Unraveling the function of the many genes that encode for uncharacterized open reading frames (ORFs) is important to understand physiological processes. Methods: By whole exome sequencing, yeast-2-hybrid, transcriptome analysis and molecular characterization we could uncover the cause of an undescribed mitochondriopathy. Results: We ide...
Article
We present a male infant with alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and macrosomia/macrocephaly at birth. Whole-exome sequencing revealed a homozygous 2bp-insertion in the latent transforming growth factor-beta binding protein 2 (LTBP2) (c.278_279dup, p.(Ser94Glyfs*187)). So far, LTBP2...
Article
Full-text available
Background & Aims Aberrant lymphocyte homing could potentially link inflammatory processes in the intestine and the liver, as distinct hepatobiliary diseases frequently develop as extra-intestinal manifestations in inflammatory bowel disease. In this study, we examined the role of the gut-tropic leukocyte adhesion molecule β7 integrin and its endot...
Article
Full-text available
The transcription factor Nrf2 regulates oxidative stress responses. However, the specific function of Nrf2 in regulatory T cells (Treg), the central regulators of immune homeostasis, is unclear. Here we report an unexpected but important role of Nrf2 in Tregs. Nrf2 expression driven by Foxp3 specific deletion of Keap1 resulted in an autoinflammator...
Article
Full-text available
Abstract Neonatal sepsis is accompanied by impaired apoptotic depletion of monocytes and macrophages (MΦ), aberrant cytokine production, impaired cell metabolism, and sustained inflammation. Macrophage-colony stimulating factor (M-CSF) triggers the differentiation from monocytes into MΦ (MΦ-0). Interleukin-10 (IL10) and Interferon-gamma (IFNy) furt...
Article
Objective: Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. Methods: Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event...
Article
Full-text available
Systemic lupus erythematosus (SLE) is an autoimmune disease and lupus nephritis is a major risk factor for morbidity and mortality. Notch-3 signaling induced by membrane-bound or soluble ligands such as YB-1 constitutes an evolutionarily conserved pathway that determines major decisions in cell fate. Mass spectrometry of extracellular YB-1 in sera...
Article
Full-text available
Background: Allergic diseases and especially allergic asthma are widespread diseases with high prevalence in childhood, but also in adults. Acid sphingomyelinase (ASM) is a key regulator of the sphingolipid pathway. Previous studies defined the association of ASM with the pathogenesis of TH 1-directed lung diseases like cystic fibrosis and acute l...
Article
Obstructive lung diseases are the most common childhood pulmonary diseases. Bronchial asthma is the most common chronic pulmonary disease of childhood. In pediatric bronchial asthma there are clear S2 guidelines for diagnosis and therapy, which can also be carried out by the treating pediatrician. RSV-related bronchiolitis is a potentially life-thr...
Article
Full-text available
Neonatal sepsis is characterized by hyperinflammation causing enhanced morbidity and mortality compared to adults. This suggests differences in the response towards invading threats. Here we investigate activated cord blood macrophages (CBMΦ) in comparison to adult macrophages (PBMΦ), indicating incomplete interferon gamma (IFN-γ) and interleukin 1...
Article
Full-text available
Autoimmune and auto-inflammatory diseases in children are causing chronic inflammation, organ damage, and pain. Although several options for treatment are nowadays available a significant number of patients does not respond sufficiently to current therapies. In these diseases inflammatory processes are triggered by numerous exogenous and endogenous...
Article
Full-text available
Background The acute respiratory distress syndrome (ARDS) is a serious disease in critically ill patients that is characterized by pulmonary dysfunctions, hypoxemia and significant mortality. Patients with immunodeficiency (e.g. SCID with T and B cell deficiency) are particularly susceptible to the development of severe ARDS. However, the role of T...
Article
Full-text available
Reactive oxygen species (ROS) molecules are implicated in signal transduction pathways and thereby control a range of biological activities. Immune cells are constantly confronted with ROS molecules under both physiologic and pathogenic conditions. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive, immature myeloid cells and serve as m...
Article
Full-text available
Arising in inflammatory conditions, myeloid-derived suppressor cells (MDSCs) are constantly confronted with intracellular and extracellular reactive oxygen species molecules and oxidative stress. Generating mice with a constitutive activation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) we show a pivotal role of the antioxidant stress defe...
Article
Objectives To study JIA long‐term outcomes in relation to the time of biological (b)DMARD initiation. Methods Outcomes of JIA patients prospectively followed by the BiKeR/JuMBO registers were analyzed with regard to i) drug‐free remission and inactive disease, ii) functional status and quality of life, iii) surgery. To analyze the influence of ear...
Article
Full-text available
Background: Inflammatory effector T cells trigger inflammation despite increased numbers of Treg cells in the synovial joint of patients suffering from juvenile idiopathic arthritis (JIA). The cAMP response element (CREM)α is known to play a major role in regulation of T cells in SLE, colitis, and EAE. However, its role in regulation of effector T...
Article
Full-text available
Background: The term systemic juvenile idiopathic arthritis (sJIA) describes an autoinflammatory condition characterized by arthritis and severe systemic inflammation, which in later stages can transform into interleukin (IL)-17-driven autoimmune arthritis. IL-1 antagonists have been used with good efficacy in the early stages of sJIA. Methods:...
Article
Full-text available
Dendritic cells (DCs) are crucial for the balance between immune response and tolerance, but the molecular mechanism regulating development, differentiation, and homeostasis are poorly understood. The transcriptional activator CREB is involved in regulating different cells of the innate and adaptive immune system and is a transcriptional regulator...
Article
Kollagenosen sind systemische Autoimmunerkrankungen, die verschiedene Organe betreffen können. Die Krankheitsbilder umfassen den systemischen Lupus erythematodes, die Dermatomyositis, die systemische Sklerose, das Sjögren-Syndrom, „Overlap“-Syndrome und undifferenzierte Kollagenosen. Aufgrund ihrer Seltenheit und ihrer Schwere stellen Kollagenosen...
Article
Full-text available
Background: Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. Thi...
Article
Full-text available
Background/aims: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naiv...
Article
Full-text available
Background: Drug hypersensitivity reactions of immediate type pose a challenging problem, especially, if standard diagnostic procedures do not lead to conclusive results. The aim of this investigation is to identify, whether basophil activation test (BAT) is able to provide additional benefit in the diagnostic evaluation of immediate type drug hype...
Article
Full-text available
Background: Electrical impedance tomography (EIT) provides information on global and regional ventilation during tidal breathing and mechanical ventilation. During forced expiration maneuvers, the linearity of EIT and spirometric data has been documented in healthy persons. The present study investigates the potential diagnostic use of EIT in pedia...
Article
Full-text available
This paper describes a novel extension of the Forced Oscillation Technique (FOT), namely the volume-dependent Forced Oscillation Technique (v-FOT). This extension is based on the measurement of the respiratory impedance over the whole lung volume. A new measurement protocol was introduced: subjects breathe slowly from residual volume to total lung...
Article
Full-text available
Click here for the corresponding questions to this CME article.
Chapter
Das Kapitel der Atemwegserkrankungen behandelt zunächst die wichtigsten angeborenen Fehlbildungen. Zu den Erkrankungen des oberen Respirationstraktes gehören die Otitis media, Mastoiditis, Pharyngitis, Tonsillitis sowie Adenoide. Erkrankungen der unteren Atemwege, die am häufigsten im Kindesalter auftreten, sind Pseudokrupp, Epiglottitis, Bronchiti...
Data
P368 Introduction: Idiopathic musculoskeletal pain (IMP) is related to a negative impact in the quality of life of children and adolescents sleep problems and psychosocial factors seem to be involved in its pathogenesis, which is not fully known. Restless legs syndrome (RLS), periodic limb movements (PML) and sleep problems were observed in adults...
Article
Objectives: Aortopexy is widely used; however, many surgeons still regard it with suspicion. To date, there are only a few large series and minimal long-term data. Against this background, our goal was to report our experience, particularly with regard to the recent expansion of indications and modification of diagnostic routine and surgical strat...
Article
Full-text available
Electrical impedance tomography (EIT) provides global and regional information about ventilation by means of relative changes in electrical impedance measured with electrodes placed around the thorax. In combination with lung function tests, e.g. spirometry and body plethysmography, regional information about lung ventilation can be achieved. Imped...
Article
Full-text available
Background: Asthma in childhood has a prevalence of 5-10% in Germany and severe asthma accounts for about 5% in this patient group. Positive predictive values for severe asthma are atopy, a positive family history and sensitizations against inhalative allergens. Alternaria is an important inhalative allergen and sensitization is suspected to corre...
Article
Deficiency of adenosine deaminase 2 (ADA2) due to homozygous or compound heterozygous mutations in the cat eye syndrome chromosome region, candidate 1 (CECR1) gene causes an autoimmune phenotype with systemic vasculitis affecting the skin, inner organs, and the central nervous system. Typically, stroke has been reported to follow systemic inflammat...