Publications by authors named "Philipp Kolb"

Objective: The high potential of CD19.CAR-T cells to treat autoimmune diseases such as Systemic Sclerosis (SSc) supposedly relies on the disappearance of autoantibodies. Here we investigated effects of CAR-T cells on the innate immune system which is an important contributor to pathology in SSc.

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COVID-19-related critical and acute illness are associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other healthcare professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness, acute illness, and those being discharged from the hospital, who do not have suspected or confirmed VTE. ASH formed a multidisciplinary panel, including three patient representatives, and applied a conflicts of interest management policy to minimize potential bias.

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We report direct measurements of the magnetic field screening at the limits of the Meissner phase for two superconducting niobium (Nb) samples. The samples are processed with two different surface treatments that have been developed for superconducting radio-frequency (SRF) cavity applications-a "baseline" treatment and an oxygen-doping ("O-doping") treatment. The measurements show: (1) that the screening length is significantly longer in the "O-doping" sample compared to the "baseline" sample; (2) that the screening length near the limits of the Meissner phase increases with applied field; (3) the evolution of the screening profile as the material transitions from the Meissner phase to the mixed phase; and (4) a demonstration of the absence of any screening profile for the highest applied field, indicative of the full flux entering the sample.

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Objective: Previous technical limitations prevented the proof of Fcγ-receptor (FcγR)-activation by soluble immune complexes (sICs) in patients. FcγRIIIa (CD16) is a risk factor in rheumatoid arthritis (RA). We aimed at determining the presence of CD16-activating sICs in RA and control diseases.

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Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation , but their role in infection and pathogenesis is unknown. To examine the function of vFcγRs in animal hosts closely related to humans, we identified and characterized vFcγRs encoded by rhesus CMV (RhCMV). We demonstrate that Rh05, Rh152/151 and Rh173 represent the complete set of RhCMV vFcγRs, each displaying functional similarities to their respective HCMV orthologs with respect to antagonizing host FcγR activation .

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Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients.

Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients.

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Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients.

Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients.

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Article Synopsis
  • - Monoclonal antibodies targeting the spike protein of SARS-CoV-2, like the REGN-COV cocktail, are useful in treating high-risk patients but can lead to viral mutations in those with compromised immune systems.
  • - In a kidney transplant patient with low antibody levels, the virus failed to clear after mAb treatment, and it developed three mutations that allowed it to escape neutralization.
  • - The eventual virus clearance occurred after adjusting the patient's immunosuppressive medication, suggesting that reducing immunosuppression may help overcome the viral adaptations caused by mAb treatment.
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A new high field spectrometer has been built to extend the capabilities of the β-detected nuclear magnetic resonance (β-NMR) facility at TRIUMF. This new beamline extension allows β-NMR spectroscopy to be performed with fields up to 200 mT parallel to a sample's surface (perpendicular to the ion beam), allowing depth-resolved studies of local electromagnetic fields with spin polarized probes at a much higher applied magnetic field than previously available in this configuration. The primary motivation and application is to allow studies of superconducting radio frequency (SRF) materials close to the critical fields of Nb metal, which is extensively used to fabricate SRF cavities.

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Article Synopsis
  • Severe COVID-19 patients exhibit a dysfunctional immune response characterized by high levels of SARS-CoV-2 specific IgG antibodies that can lead to harmful effects rather than protection.
  • The study identifies a significant activation of FcγRIIIA/CD16A in severely impacted patients, which is linked to the presence of soluble circulating IgG immune complexes (sICs) found in about 80% of these cases.
  • The early formation of sICs before a specific immune response may be causing ongoing immunopathology, suggesting potential new intervention strategies to help those at risk of critical COVID-19 progression.
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The genome of cowpoxvirus (CPXV) could be considered prototypical for orthopoxviridae (OXPV) since it contains many open reading frames (ORFs) absent or lost in other OPXV, including vaccinia virus (VACV). These additional ORFs are non-essential for growth in vitro but are expected to contribute to the broad host range, virulence and immune evasion characteristics of CPXV. For instance, unlike VACV, CPXV encodes proteins that interfere with T cell stimulation, either directly or by preventing antigen presentation or co-stimulation.

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Infection with the pandemic human coronavirus SARS-CoV-2 elicits a respiratory tract disease, termed Coronavirus disease 2019 (COVID-19). While a variable degree of disease-associated symptoms may emerge, severe COVID-19 is commonly associated with respiratory complications such as acute respiratory distress syndrome (ARDS), the necessity for mechanical ventilation or even extracorporeal membrane oxygenation (ECMO). Amongst others, disease outcome depends on age and pre-existing conditions like cardiovascular diseases, metabolic disorders but also age and biological sex.

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In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries.

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Fc-gamma receptor (FcγR) activation by soluble IgG immune complexes (sICs) represents a major mechanism of inflammation in certain autoimmune diseases such as systemic lupus erythematosus (SLE). A robust and scalable test system allowing for the detection and quantification of sIC bioactivity is missing. We developed a comprehensive reporter cell panel detecting activation of FcγRs.

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Background: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE).

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE.

Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest.

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Background: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE).

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE.

Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest.

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Objective: Findings from recent transcriptome analyses of the synovium of patients with rheumatoid arthritis (RA) have revealed that 15-fold expanded HLA-DR+CD90+ synovial fibroblasts potentially act as key mediators of inflammation. The reasons for the expansion of HLA-DR+CD90+ synovial fibroblasts are unclear, but genetic signatures indicate that interferon-γ (IFNγ) plays a central role in the generation of this fibroblast subset. The present study was undertaken to investigate the generation, function and therapeutically intended blockage of HLA-DR+CD90+ synovial fibroblasts.

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Objectives: To compare different modalities of renal replacement therapy in critically ill adults with acute kidney injury.

Data Sources: We searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 25 May, 2020.

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Article Synopsis
  • Human cytomegalovirus (HCMV) uses advanced immune evasion strategies to avoid being targeted by the host's immune system, particularly through antibody-dependent cellular cytotoxicity (ADCC).
  • The viral proteins gp34 and gp68 bind to immunoglobulin G (IgG) at different sites, which helps HCMV to effectively disrupt the host immune response.
  • Together, gp34 enhances the internalization of immune complexes, while gp68 inhibits host receptors from binding to these complexes, showcasing a cooperative mechanism that impairs the host's immune recognition and function.
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Background: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE).

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE.

Methods: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest.

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Pulmonary fibrosis is a progressive lung disease characterized by myofibroblast accumulation and excessive extracellular matrix deposition. We sought to investigate the role of FKBP13 (13-kD FK506-binding protein), an endoplasmic reticulum-resident molecular chaperone, in various forms of pulmonary fibrosis. We first characterized the gene and protein expression of FKBP13 in lung biopsy specimens from 24 patients with idiopathic pulmonary fibrosis and 17 control subjects.

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Idiopathic pulmonary fibrosis (IPF) is a complex disease of unknown aetiology, which makes drug development challenging. Single administration of bleomycin directly to the lungs of mice is a widely used experimental model for studying pulmonary fibrogenesis and evaluating the effect of therapeutic antifibrotic strategies. The model works by inducing an early inflammatory phase, which transitions into fibrosis after 5-7 days.

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Receptors recognizing the Fc part of immunoglobulin G (FcγRs) are key determinants in antibody-mediated immune responses. Members of the interfere with this immune regulatory network by expressing viral FcγRs (vFcγRs). Human cytomegalovirus (HCMV) encodes four distinct vFcγRs that differ with respect to their IgG subtype specificity and their impact on antibody-mediated immune function The impact of vFcγRs on HCMV pathogenesis and immunomodulation is not known.

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