Clinical ischemia-reperfusion injury: Driven by reductive rather than oxidative stress? A narrative review.

Ischemia-reperfusion (IR) injury remains a major contributor to organ dysfunction following transient ischemic insults. Although numerous interventions have been found effective to reduce IR injury in preclinical models, none of these therapies have been successfully translated to the clinical setting. In the context of the persistent translational gap, we systematically investigated the mechanisms implicated in IR injury using kidney donation and transplantation as a clinical model of IR.

Enrichment of serum IgG4 in MuSK myasthenia gravis patients.

Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular autoimmune disease belonging to a growing group of IgG4 autoimmune diseases (IgG4-AIDs), in which the majority of pathogenic autoantibodies are of the IgG4 subclass. The more prevalent form of MG with acetylcholine receptor (AChR) antibodies is caused by IgG1-3 autoantibodies. A dominant role for IgG4 in autoimmune disease is intriguing due to its anti-inflammatory characteristics.

Antineutrophil cytoplasmic antibodies in infective endocarditis: a case report and systematic review of the literature.

Infective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial to guide therapy. However, little is known about ANCA positivity in IE patients.

Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1.

Study Objectives: The diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111-200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.

Methods: Retrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands.

Hypocretin-1 measurements in cerebrospinal fluid using radioimmunoassay: within and between assay reliability and limit of quantification.

Study Objectives: The most sensitive and specific investigative method for the diagnosis of narcolepsy type 1 (NT1) is the determination of hypocretin-1 (orexin-A) deficiency (≤110 pg/mL) in cerebrospinal fluid using a radioimmunoassay (RIA). We aimed to assess the reliability of the Phoenix Pharmaceuticals hypocretin-1 RIA, by determining the lower limit of quantification (LLOQ), the variability around the cutoff of 110 pg/mL, and the inter- and intra-assay variability.

Methods: Raw data of 80 consecutive hypocretin-1 RIAs were used to estimate the intra- and inter-assay coefficient of variation (CV).

Biomarkers to identify infection among borderline QuantiFERON results.

Background: Screening for tuberculosis (TB) infection often includes QuantiFERON-TB Gold Plus (QFT) testing. Previous studies showed that two-thirds of patients with negative QFT results just below the cut-off, so-called borderline test results, nevertheless had other evidence of TB infection. This study aimed to identify a biomarker profile by which borderline QFT results due to TB infection can be distinguished from random test variation.

Preclinical models versus clinical renal ischemia reperfusion injury: A systematic review based on metabolic signatures.

Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing toward a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function) identified metabolic derailment as a key driver of renal IR injury. It was reasoned that these unambiguous metabolic findings enable direct alignment of clinical with preclinical data, thereby providing the opportunity to elaborate potential translational hurdles between preclinical research and the clinical context.

Anticentromere Antibody Levels and Isotypes and the Development of Systemic Sclerosis.

Objective: Little is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA-positive patients are associated with disease severity and/or progression from very early SSc to definite SSc.

Metabolic needs of the kidney graft undergoing normothermic machine perfusion.

Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy. During NMP, the organ is maintained in a metabolically active state that may not only provide superior organ preservation, but that also facilitates viability testing before transplantation, and ex situ resuscitation of marginal kidney grafts. Although the prevailing perfusion protocols for renal NMP are refined from initial pioneering studies concerning short periods of NMP, it could be argued that these protocols are not optimally tailored to address the putatively compromised metabolic plasticity of marginal donor grafts (i.

Circumventing the Crabtree effect in cell culture: A systematic review.

Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established itself as a versatile technique for the elaboration of physiology and disease, studying metabolism using standard cell culture protocols is profoundly interfered by the Crabtree effect. This phenomenon refers to the adaptation of cultured cells to a glycolytic phenotype, away from oxidative phosphorylation in glucose-containing medium, and questions the applicability of cell culture in certain fields of research.

Plasma Amino Acid Concentrations at Birth and Patent Ductus Arteriosus in Very and Extremely Preterm Infants.

Amino acids are increasingly recognized as bioactive molecules in numerous physiological and pathophysiological pathways. The non-essential amino acid glutamate is vasoactive in the rat ductus arteriosus (DA) and a decrease in its levels within the 1st days of life has been associated with the presence of patent DA (PDA) in extremely preterm infants. However, these findings have not been confirmed in other studies.

Association of Anti-Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti-Topoisomerase I-Positive Systemic Sclerosis.

Objective: Anti-topoisomerase I (anti-topo I) autoantibodies in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relationship between anti-topo I antibody response and disease course has not yet been fully evaluated. This study was undertaken to gain insight into the association between characteristics of the anti-topo I antibody response and clinical disease course in SSc patients positive for anti-topo I antibodies.

Results of an explorative clinical evaluation suggest immediate and persistent post-reperfusion metabolic paralysis drives kidney ischemia reperfusion injury.

Delayed graft function is the manifestation of ischemia reperfusion injury in the context of kidney transplantation. While hundreds of interventions successfully reduce ischemia reperfusion injury in experimental models, all clinical interventions have failed. This explorative clinical evaluation examined possible metabolic origins of clinical ischemia reperfusion injury combining data from 18 pre- and post-reperfusion tissue biopsies with 36 sequential arteriovenous blood samplings over the graft in three study groups.

Frequencies and clinical associations of myositis-related antibodies in The Netherlands: A one-year survey of all Dutch patients.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of connective tissue diseases, collectively known as myositis. Diagnosis of IIM is challenging while timely recognition of an IIM is of utter importance considering treatment options and otherwise irreversible (severe) long-term clinical complications. With the EULAR/ACR classification criteria (2017) considerable advancement has been made in the diagnostic workup of IIM.

PR3-ANCAs predict relapses in ANCA-associated vasculitis patients after rituximab.

Background: The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI).

Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results.

Background: Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF).

Association Between Centromere- and Topoisomerase-specific Immune Responses and the Degree of Microangiopathy in Systemic Sclerosis.

Objective: Autoreactive antibody responses, including the use of several isotypes of autoantibodies, have been shown to be associated with clinical outcome in several rheumatic autoimmune diseases. The goals of this study were to evaluate whether (1) anticentromere antibody (ACA)- and antitopoisomerase antibody (ATA)-specific isotype expression, and (2) organ involvement are associated with the degree of microangiopathy in systemic sclerosis (SSc).

Methods: ACA and ATA IgG, IgM, and IgA levels were measured in baseline serum samples of ACA IgG-positive (+) and ATA IgG+ patients with SSc.

Trends in diagnostic methods and treatment of latent tuberculosis infection in a tertiary care center from 2000 to 2017.

Screening for latent tuberculosis infection (LTBI) is indicated before immunosuppressive therapies but is complicated by lack of a gold standard and limited by, e.g., immunosuppression.

A reverse translational study on the effect of rituximab, rituximab plus belimumab, or bortezomib on the humoral autoimmune response in SLE.

Objectives: SLE is a severe autoimmune disease characterized by autoreactive B cells and IC formation, which causes systemic inflammation. B cell-targeted therapy could be a promising treatment strategy in SLE patients; nevertheless, randomized clinical trials have not always been successful. However, some groups have demonstrated beneficial effects in severe SLE patients with off-label rituximab (RTX) with belimumab (BLM), or bortezomib (BTZ), which targeted different B cells subsets.

Abnormalities suggestive of latent tuberculosis infection on chest radiography; how specific are they?

Background: Several radiological features have been reported in association with latent tuberculosis infection (LTBI) but it has not been studied which are specific. The aim of this study was to evaluate allegedly characteristic abnormalities on chest radiography (CXR) in patients with LTBI compared to uninfected controls.

Methods: From 236 patients tested with QuantiFERON-TB Gold In-Tube (QFT), the CXR was re-evaluated in a blinded fashion for fibrotic scarring, (non-)calcified nodules and pleural thickening.

Intrinsically Distinct Role of Neutrophil Extracellular Trap Formation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Compared to Systemic Lupus Erythematosus.

Objective: Different studies have demonstrated that neutrophil extracellular traps (NETs) may be involved in the pathophysiology of both antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). AAV and SLE are clinically and pathologically divergent autoimmune diseases with different autoantibodies. However, the respective autoantigens recognized in AAV and SLE have been shown to be an intricate part of NETs.

A prospective, double-blind, randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis.

Objective: To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).

Methods: An influenza vaccination or placebo was administered to 47 AChR MG patients. Before and 4 weeks after administration blood samples and clinical outcome scores were obtained.

Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy.

The HIV-human metabolic relationship is a complex interaction convoluted even more by antiretroviral therapy (cART) and comorbidities. The ability of cART to undo the HIV induced metabolic dysregulation is unclear and under-investigated. Using targeted metabolomics and multiplex immune biomarker analysis, we characterized plasma samples obtained from 18 untreated HIV-1-infected adult patients and compared these to a non-HIV infected (n = 23) control population.