Background: Little is known about the symptoms at the onset of Sjögren's Disease (SjD) and it is unclear whether SjD starts with characteristic symptoms that could be differentiated from dryness of other origin (sicca syndrome). The aim of this study was to investigate patients' recollection of initial events and first symptoms of SjD. The second aim was to verify and quantify these aspects in a representative cohort.
View Article and Find Full Text PDFGlucose metabolism is a critical regulator of T cell function, largely thought to support their activation and effector differentiation. Here, we investigate the relevance of individual glycolytic reactions in determining the pathogenicity of T helper 17 (Th17) cells using single-cell RNA-seq and Compass, an algorithm we previously developed for estimating metabolic flux from single-cell transcriptomes. Surprisingly, Compass predicted that the metabolic shunt between 3-phosphoglycerate (3PG) and 2-phosphoglycerate (2PG) is inversely correlated with pathogenicity in these cells, whereas both its upstream and downstream reactions were positively correlated.
View Article and Find Full Text PDFAdverse drug reactions frequently involve the gastrointestinal tract. We present two cases of colitis that occurred months to years after chemotherapy and autologous stem cell transplantation for the treatment of lymphoma. Laboratory tests revealed altered immune status with decreased CD4/CD8 ratio and hypogammaglobinemia (in one patient).
View Article and Find Full Text PDFAn efficient and general cascade synthesis of pyrroles from nitroarenes using an acid-tolerant homogeneous iron catalyst is presented. Initial (transfer) hydrogenation using the commercially available iron-Tetraphos catalyst is followed by acid catalysed Paal-Knorr condensation. Both formic acid and molecular hydrogen can be used as green reductants in this process.
View Article and Find Full Text PDFBiradicals are important intermediates in the process of bond formation and breaking. While main-group-element-centered biradicals have been thoroughly studied, much less is known about tetraradicals, as their very low stability has hampered their isolation and use in small-molecule activation. Herein, we describe the search for persistent phosphorus-centered tetraradicals.
View Article and Find Full Text PDFB-cell depleting therapies result in diminished humoral immunity following vaccination against COVID-19, but our understanding on the impact on cellular immune responses is limited. Here, we performed a detailed analysis of cellular immunity following mRNA vaccination in patients receiving B-cell depleting therapy using ELISpot assay and flow cytometry. Anti-SARS-CoV-2 spike receptor-binding domain antibody assays were performed to elucidate B-cell responses.
View Article and Find Full Text PDFManganese-catalyzed hydrogenation reactions have aroused widespread interest in recent years. Among the catalytic systems described, especially PNP- and NNP-Mn pincer catalysts have been reported for the hydrogenation of aldehydes, ketones, nitriles, aldimines and esters. Furthermore, NNP-Mn pincer compounds are efficient catalysts for the hydrogenolysis of less reactive amides, ureas, carbonates, and carbamates.
View Article and Find Full Text PDFA phosphine-oxide-promoted, cobalt-catalysed reductive etherification using syngas as a reductant is reported. This novel methodology was successfully used to prepare a broad range of unsymmetrical ethers from various aldehydes and alcohols containing diverse functional groups, and was scaled-up to multigram scale under comparably mild conditions. Mechanistic experiments support an acetalization-hydrogenation sequence.
View Article and Find Full Text PDFImmunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine.
View Article and Find Full Text PDFImmunosenescence is a state of dysregulated leukocyte function characterised by arrested cell cycle, telomere shortening, expression of markers of cellular stress, and secretion of pro-inflammatory mediators. Immunosenescence principally develops during aging, but it may also be induced in other pathological settings, such as chronic viral infections and autoimmune diseases. Appearance of senescent immune cells has been shown to potentially cause chronic inflammation and tissue damage, suggesting an important role for this process in organismal homeostasis.
View Article and Find Full Text PDFObjective: To compare structural findings between US, micro-CT (µCT) and histology in people with OA of the hands.
Methods: We analysed DIP and PIP joints of 31 fingers from 15 dissecting-room cadavers with OA of the hands. The occurrence of bone erosions and osteophytes were recorded by US, µCT and histology at 16 regions for each joint and compared for each method.
Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T cell (Treg) differences, which we validated by metabolic assays.
View Article and Find Full Text PDFBackground And Purpose: The outbreak of the COVID-19 pandemic has resulted in an overall decline in fractures. However, the amount of hip fractures has remained relatively stable throughout the period. The objective of this study is to investigate the impact of perioperative COVID-19 infections on mortality among hip fracture patients.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic. Cytokine release syndrome occurring in a minority of SARS-CoV-2 infections is associated with severe disease and high mortality. We profiled the composition, activation, and proliferation of T cells in 20 patients with severe or critical COVID-19 and 40 matched healthy controls by flow cytometry.
View Article and Find Full Text PDFObjective: To investigate peripheral lymphopenia, a frequent finding in primary Sjögren's syndrome (pSS) associated with higher disease activity and increased mortality.
Methods: Prospective, cross-sectional study of consecutive patients with pSS (n = 66) and healthy controls (n = 181). Lymphocyte subsets were analysed by flow cytometry, naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology.
Mult Scler J Exp Transl Clin
September 2018
Background: The increasing armamentarium of disease-modifying therapies in multiple sclerosis is accompanied by potentially severe adverse effects. The cell-adhesion molecule CD62L, which facilitates leukocyte extravasation, has been proposed as a predictive marker for treatment tolerability. However, pre-analytical procedures might impact test results, thereby limiting its clinical usability.
View Article and Find Full Text PDFObjective: T-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid arthritis (RA). Premature senescence of lymphocytes including the accumulation of senescent CD4 T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far.
View Article and Find Full Text PDFObjective: Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression.
View Article and Find Full Text PDFA disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders.
View Article and Find Full Text PDFObjective: To investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA).
Methods: Prospective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) and CD8(+) T-cell subsets by MACS technology.