Hybrid Immunity Protects against Antibody Fading after SARS-CoV-2mRNA Vaccination in Kidney Transplant Recipients, Dialysis Patients, and Medical Personnel: 9 Months Data from the Prospective, Observational Dia-Vacc Study.

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR).

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

Background: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients.

Methods: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks.

Findings: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively.

Pleuroparenchymal Fibroelastosis: A Review with a Focus on a Non-Infectious Complications after Hematopoietic Stem Cell Transplant.

Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that is currently classified as an idiopathic interstitial pneumonia. Although originally described as an idiopathic disease, PPFE has now been identified as a rare complication following hematopoietic stem cell transplant (HSCT). Unlike other pulmonary complications after HSCT, PPFE occurs very late after transplant.

A quantitative 3D intravital look at the juxtaglomerular renin-cell-niche reveals an individual intra/extraglomerular feedback system.

The juxtaglomerular niche occupied by renin cells (RCN) plays an important role in glomerular repair but the precise temporal and spatial interrelations remain unclear. This study proposes the hypothesis of a local intra-extraglomerular regenerative feedback system and establishes a new quantifiable system for RCN responses in individual glomeruli . A strictly intraglomerular two-photon laser-induced injury model was established.

MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination.

Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination.

Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion ( IgA or IgG antibody positivity by ELISA) after eight weeks.

Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR ( = 0·005), respectively.

Cellular and Humoral Immune Responses After 3 Doses of BNT162b2 mRNA SARS-CoV-2 Vaccine in Kidney Transplant.

Supplemental Digital Content is available in the text.

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

Background: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.

Methods: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273.

Results: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%).

Lethal hyperammonemia in a CAR-T cell recipient due to pneumonia: a case report of a unique severe complication.

We report the first incidence of infection causing lethal hyperammonemia in a chimeric receptor antigen T cell (CAR-T) recipient. A 53-year-old woman, after receiving CAR-T therapy, suffered sepsis and encephalopathy. She was found to have hyperammonemia up to 643 µmol/L.

Expression of components of the urothelial cholinergic system in bladder and cultivated primary urothelial cells of the pig.

Background: Porcine urinary bladders are widely used for uro-pharmacological examinations due to their resemblance to the human organ. However, characterisations of the porcine urothelium at the molecular level are scarce up to now. As it has become clear over the last years that this tissue plays an important role in the signaling-pathways of the bladder, we examined whether the transporter and receptor pattern (with focus on the transmitter acetylcholine) is comparable to the human urothelium.

The Rare Complication and Diagnostic Challenges of Pulmonary Eosinophilia in Graft versus Host Disease Patients after Hematopoietic Stem Cell Transplantation.

Purpose: Chronic graft versus host disease (cGvHD) is a common complication of hematopoietic stem cell transplantation (HSCT). Eosinophilic lung disease is a rare poorly understood complication in HSCT patients with cGvHD. These patients present similarly to those with Acute Eosinophilic Pneumonia (AEP).

Mechanical induction of bi-directional orientation of primary porcine bladder smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for ureteral and urethral repair using cyclic and focal balloon catheter stimulation.

To restore damaged organ function or to investigate organ mechanisms, it is necessary to prepare replicates that follow the biological role model as faithfully as possible. The interdisciplinary field of tissue engineering has great potential in regenerative medicine and might overcome negative side effects in the replacement of damaged organs. In particular, tubular organ structures of the genitourinary tract, such as the ureter and urethra, are challenging because of their complexity and special milieu that gives rise to incrustation, inflammation and stricture formation.

A 66-Year-Old Woman With Sudden Onset of Disseminated Intravascular Coagulation, Lactic Acidosis, and Hypoglycemia.

A 66-year-old woman presented to an urgent care clinic for 2 to 3 weeks of general malaise, nausea/vomiting, night sweats, and dyspnea. On examination, she was tachycardic, and her laboratory evaluation was normal except for a lactate level of 4.4 mmol/L and platelet count of 118 × 10/L.

Leukocyte ADAM17 regulates acute pulmonary inflammation.

The transmembrane protease ADAM17 regulates the release and density of various leukocyte cell surface proteins that modulate inflammation, including L-selectin, TNF-α, and IL-6R. At this time, its in vivo substrates and role in pulmonary inflammation have not been directly examined. Using conditional ADAM17 knock-out mice, we investigated leukocyte ADAM17 in acute lung inflammation.

c-Jun NH2-terminal kinase regulates lipopolysaccharide-induced pulmonary mononuclear cell recruitment via CCL2.

Subsequent to the initial recruitment of neutrophils, monocytes are recruited to the lung after an injurious insult. Previously the authors have shown that inhibition of either p38 or c-Jun NH(2)-terminal kinase (JNK) decreased pulmonary neutrophil recruitment in mice exposed to lipopolysaccharide (LPS). As the signaling pathways regulating the influx of mononuclear cells to the lung are poorly understood, the authors undertook the present study to examine the roles of p38 and JNK.

Tec kinases regulate actin assembly and cytokine expression in LPS-stimulated human neutrophils via JNK activation.

The acute inflammatory response involves neutrophils wherein recognition of bacterial products, such as lipopolysaccharide (LPS), activates intracellular signaling pathways. We have shown that the mitogen-activated protein kinase (MAPK) c-Jun NH(2) terminal kinase (JNK) is activated by LPS in neutrophils and plays a critical role in monocyte chemoattractant protein (MCP)-1 expression and actin assembly. As the Tec family kinases are expressed in neutrophils and regulate activation of the MAPKs in other cell systems, we hypothesized that the Tec kinases are an upstream component of the signaling pathway leading to LPS-induced MAPKs activation in neutrophils.

Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccharide-induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways.

Recruitment of neutrophils to the lung is a sentinel event in acute lung inflammation. Identifying mechanisms that regulate neutrophil recruitment to the lung may result in strategies to limit lung damage and improve clinical outcomes. Recently, the renin angiotensin system (RAS) has been shown to regulate neutrophil influx in acute inflammatory models of cardiac, neurologic, and gastrointestinal disease.

Dual role for RhoA in suppression and induction of cytokines in the human neutrophil.

Production of tumor necrosis factor-alpha (TNFalpha) by the neutrophil (PMN) is a pivotal event in innate immunity, but the signals regulating TNFalpha induction in this primary cell are poorly understood. Herein, we use protein transduction to identify novel, opposing anti- and pro-cytokine-inducing roles for RhoA in the resting and lipopolysaccharide (LPS)-stimulated human PMN, respectively. In the resting cell, RhoA suppresses Cdc42 activation, IkappaBalpha degradation, nuclear factor-kappaB (NF-kappaB) activation, and induction of TNFalpha and NF-kappaB-dependent chemokines.

Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa.

Bacterial pneumonia is a leading cause of mortality and is associated with extensive neutrophil accumulation. Major pathogens associated with this disease include nonflagellated Klebsiella pneumoniae (Kp) and flagellated Pseudomonas aeruginosa (Pa). TLRs are essential for innate immune defense.

Regulation of lipopolysaccharide-induced lung inflammation by plasminogen activator Inhibitor-1 through a JNK-mediated pathway.

The neutrophil is of undoubted importance in lung inflammation after exposure to LPS. We have shown recently that systemic inhibition of JNK decreased neutrophil recruitment to the lung after exposure to LPS, although the mechanisms underlying this inhibition are incompletely understood. As plasminogen activator inhibitor-1 (PAI-1) accentuates cell migration, with JNK activation recently shown to up-regulate PAI-1 expression, this suggested that systemic JNK inhibition may down-regulate LPS-induced pulmonary neutrophil recruitment through a decrease in PAI-1 expression.

Inhibition of c-Jun N-terminal kinase limits lipopolysaccharide-induced pulmonary neutrophil influx.

The influx of neutrophils into the lung is a sentinel event in LPS-induced acute lung inflammation. Previous studies have shown that systemic inhibition of p38 decreases LPS-induced neutrophil influx into the alveolar space but has no effect on pulmonary parenchymal neutrophil accumulation or on microvascular leak, indicating other pathways are important in LPS-induced acute lung inflammation. This study examined the role of c-Jun N-terminal kinase in LPS-induced acute lung inflammation.

A role for hydroxy-methylglutaryl coenzyme a reductase in pulmonary inflammation and host defense.

Rationale: A growing literature indicates that hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) modulate proinflammatory cellular signaling and functions. No studies to date, however, have addressed whether statins modulate pulmonary inflammation triggered by aerogenic stimuli or whether they affect host defense.

Objectives: To test whether lovastatin modulates LPS-induced pulmonary inflammation and antibacterial host defense.

Lipid rafts regulate lipopolysaccharide-induced activation of Cdc42 and inflammatory functions of the human neutrophil.

Lipid rafts are cholesterol-rich membrane microdomains that are thought to act as coordinated signaling platforms by regulating dynamic, agonist-induced translocation of signaling proteins. They have been described to play a role in multiple prototypical cascades, among them the lipopolysaccharide pathway, and to host multiple signaling proteins, including kinases and low molecular weight G-proteins. Here we report lipopolysaccharide-induced activation of the Rho family GTPase Cdc42, and we show its activation in the human neutrophil to be mediated by a p38 mitogen-activated protein kinase-dependent mechanism.