-
1دورية أكاديمية
المصدر: RMD Open, Vol 10, Iss 2 (2024)
مصطلحات موضوعية: Medicine
الوصف: Classification criteria have been developed for rheumatoid arthritis (RA) and other rheumatic diseases in order to gather a homogeneous patient population for clinical studies and facilitate the timely implementation of therapeutic measures. Although classification criteria are not intended to be used for diagnosis, they are frequently used to support the diagnostic process in clinical practice, including clinical decision-making. The 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for RA are capable of identifying the majority of symptomatic patients with RA already in the earliest stages of the disease who are not yet showing radiographic changes. These patients will also profit from the early implementation of therapy with disease-modifying antirheumatic drugs (DMARDs). However, the risk of misclassification is higher as compared with the former 1987 ACR criteria, which were considerably less sensitive to the recognition of patients with early RA. Of note, the presence of rheumatoid factors (RFs) and anticitrullinated protein antibodies (ACPAs) has been attributed equal weight in the 2010 ACR/EULAR criteria and may contribute up to 50% of the score needed for being classified as RA. However, while ACPAs have been proven to be the most specific serological markers of RA, the specificity of RF is moderate, especially at lower titres. This may lead to the misclassification of RF-positive patients and, consequently, the unjustified implementation of DMARD therapy. Therefore, issues arise on how comprehensive the criteria should be and whether they should be updated and adapted to findings from the past two decades that might increase both their specificity and sensitivity.
وصف الملف: electronic resource
-
2دورية أكاديمية
المؤلفون: Kris Covens, Bert Verbinnen, Britt G. de Jong, Leen Moens, Greet Wuyts, Geert Verheyen, Kris Nys, Jonathan Cremer, Stijn Smulders, Rik Schrijvers, Andreas Weinhäusel, Séverine Vermeire, Patrick Verschueren, Ellen De Langhe, Jacques J. M. van Dongen, Menno C. van Zelm, Xavier Bossuyt
المصدر: Frontiers in Immunology, Vol 14 (2023)
مصطلحات موضوعية: antibody secreting cells, CD43, CD27, plasmablast, somatic hypermutation, B lymphocyte, Immunologic diseases. Allergy, RC581-607
الوصف: Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders.Conclusionwe characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1165936/fullTest; https://doaj.org/toc/1664-3224Test
-
3دورية أكاديمية
المؤلفون: Frederik Staels, Willem Roosens, Simone Giovannozzi, Leen Moens, Jan Bogaert, Cecilia Iglesias-Herrero, Rik Gijsbers, Xavier Bossuyt, Glynis Frans, Adrian Liston, Stephanie Humblet-Baron, Isabelle Meyts, Lucas Van Aelst, Rik Schrijvers
المصدر: Frontiers in Immunology, Vol 14 (2023)
مصطلحات موضوعية: primary immunodeficiencies, STAT1 GOF, myocarditis, infectious susceptibility, chronic mucocutaneous candidiasis, Immunologic diseases. Allergy, RC581-607
الوصف: Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in an inborn error of immunity characterized by chronic mucocutaneous candidiasis, recurrent viral and bacterial infections, and diverse autoimmune manifestations. Current treatment consists of chronic antifungal therapy, antibiotics for concomitant infections, and immunosuppressive therapy in case of autoimmune diseases. More recently, treatment with Janus kinases 1 and 2 (JAK1/2) inhibitors have shown promising yet variable results. We describe a STAT1 GOF patient with an incidental finding of elevated cardiac troponins, leading to a diagnosis of a longstanding, slowly progressive idiopathic myocarditis, attributed to STAT1 GOF. Treatment with a JAK-inhibitor (baricitinib) mitigated cardiac inflammation on MRI but was unable to alter fibrosis, possibly due to the diagnostic and therapeutic delay, which finally led to fatal arrhythmia. Our case illustrates that myocarditis could be part of the heterogeneous disease spectrum of STAT1 GOF. Given the insidious presentation in our case, a low threshold for cardiac evaluation in STAT1 GOF patients seems warranted.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1095595/fullTest; https://doaj.org/toc/1664-3224Test
-
4دورية أكاديمية
المؤلفون: Glynis Frans, Doreen Dillaerts, Tom Dehaemers, Jan Van Elslande, Jonas De Leeuw, Lise Boon, Wim Maes, Nico Callewaert, Bas Calcoen, Lina Ancheva, Maaike Cockx, Nick Geukens, Kusay Arat, Rita Derua, Pieter Vermeersch, Sebastien Christian Carpentier, Xavier Bossuyt
المصدر: Frontiers in Immunology, Vol 14 (2023)
مصطلحات موضوعية: SARS-CoV-2, COVID-19, hybrid immunity, complementary determining region, vaccination, Immunologic diseases. Allergy, RC581-607
الوصف: Pre-vaccination SARS-CoV-2 infection can boost protection elicited by COVID-19 vaccination and post-vaccination breakthrough SARS-CoV-2 infection can boost existing immunity conferred by COVID-19 vaccination. Such ‘hybrid immunity’ is effective against SARS-CoV-2 variants. In order to understand ‘hybrid immunity’ at the molecular level we studied the complementarity determining regions (CDR) of anti-RBD (receptor binding domain) antibodies isolated from individuals with ‘hybrid immunity’ as well as from ‘naive’ (not SARS-CoV-2 infected) vaccinated individuals. CDR analysis was done by liquid chromatography/mass spectrometry-mass spectrometry. Principal component analysis and partial least square differential analysis showed that COVID-19 vaccinated people share CDR profiles and that pre-vaccination SARS-CoV-2 infection or breakthrough infection further shape the CDR profile, with a CDR profile in hybrid immunity that clustered away from the CDR profile in vaccinated people without infection. Thus, our results show a CDR profile in hybrid immunity that is distinct from the vaccination-induced CDR profile.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1050037/fullTest; https://doaj.org/toc/1664-3224Test
-
5دورية أكاديمية
المؤلفون: Karen Yu, Luna Dillemans, Mieke Gouwy, Helena Bessa, Mieke Metzemaekers, Erik Martens, Patrick Matthys, Xavier Bossuyt, Patrick Verschueren, Carine Wouters, Lien De Somer, Paul Proost
المصدر: Frontiers in Immunology, Vol 14 (2023)
مصطلحات موضوعية: citrullination, inflammation, joint inflammation, peptidylarginine deiminase, autoimmunity, Immunologic diseases. Allergy, RC581-607
الوصف: IntroductionPeptidylarginine deiminases (PADs) mediate citrullination, an irreversible posttranslational modification that converts arginine to citrulline residues in proteins. Rheumatoid arthritis (RA) is characterized by unique autoantibodies that recognize citrullinated peptides, which are highly specific for this disease. However, the mechanism preceding the anti-citrulline response remains largely unclear. PAD enzymes are known to fuel the autoimmune response by generating autoreactive epitopes, and sustain local synovial inflammation through neutrophil extracellular trap formation. Therefore, detecting endogenous PAD activity is important to understand the pathogenesis of arthritis.MethodsIn this study, we improved a fluorescent in vitro assay to enable endogenous PAD activity characterization in complex samples. We combine the use of an in-house synthetic, arginine-rich substrate and a negatively charged dye molecule to visualize enzyme activity.ResultsThis pioneering PAD assay allowed profiling of active citrullination in leukocytes and in local and systemic samples of an arthritis cohort. Our results reveal that RA and juvenile idiopathic arthritis (JIA) synovial fluids display similar levels of PAD activity. In contrast, citrullination was limited in joints of patients suffering from gout or Lyme’s disease. Interestingly, in blood, a higher level of extracellular citrullination was only found in anti-CCP-positive RA patients.DiscussionOur finding suggests that enhanced synovial PAD activity drives the loss in tolerance towards citrullinated proteins and that systemic citrullination may indicate the risk for developing citrulline-specific autoimmunity.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111465/fullTest; https://doaj.org/toc/1664-3224Test
-
6دورية أكاديمية
المؤلفون: Bram Decru, Jan Van Elslande, Sophie Steels, Gijs Van Pottelbergh, Lode Godderis, Bram Van Holm, Xavier Bossuyt, Johan Van Weyenbergh, Piet Maes, Pieter Vermeersch
المصدر: Frontiers in Immunology, Vol 13 (2022)
مصطلحات موضوعية: SARS-CoV-2, COVD-19 serological testing, neutralizing antibodies, vaccination, spike, IgG, Immunologic diseases. Allergy, RC581-607
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1098285/fullTest; https://doaj.org/toc/1664-3224Test
-
7دورية أكاديمية
المؤلفون: Frederik Staels, Kerstin De Keukeleere, Matias Kinnunen, Salla Keskitalo, Flaminia Lorenzetti, Michiel Vanmeert, Teresa Prezzemolo, Emanuela Pasciuto, Eveline Lescrinier, Xavier Bossuyt, Margaux Gerbaux, Mathijs Willemsen, Julika Neumann, Sien Van Loo, Anniek Corveleyn, Karen Willekens, Ingeborg Stalmans, Isabelle Meyts, Adrian Liston, Stephanie Humblet-Baron, Mikko Seppänen, Markku Varjosalo, Rik Schrijvers
المصدر: Frontiers in Immunology, Vol 13 (2022)
مصطلحات موضوعية: primary immunodeficiency, functional validation, novel mutation, Nfkb1 (p50), haploinsufficiency, Immunologic diseases. Allergy, RC581-607
الوصف: NFKB1 haploinsufficiengcy was first described in 2015 in three families with common variable immunodeficiency (CVID), presenting heterogeneously with symptoms of increased infectious susceptibility, skin lesions, malignant lymphoproliferation and autoimmunity. The described mutations all led to a rapid degradation of the mutant protein, resulting in a p50 haploinsufficient state. Since then, more than 50 other mutations have been reported, located throughout different domains of NFKB1 with the majority situated in the N-terminal Rel homology domain (RHD). The clinical spectrum has also expanded with possible disease manifestations in almost any organ system. In silico prediction tools are often used to estimate the pathogenicity of NFKB1 variants but to prove causality between disease and genetic findings, further downstream functional validation is required. In this report, we studied 2 families with CVID and two novel variants in NFKB1 (c.1638-2A>G and c.787G>C). Both mutations affected mRNA and/or protein expression of NFKB1 and resulted in excessive NLRP3 inflammasome activation in patient macrophages and upregulated interferon stimulated gene expression. Protein-protein interaction analysis demonstrated a loss of interaction with NFKB1 interaction partners for the p.V263L mutation. In conclusion, we proved pathogenicity of two novel variants in NFKB1 in two families with CVID characterized by variable and incomplete penetrance.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.973543/fullTest; https://doaj.org/toc/1664-3224Test
-
8دورية أكاديمية
المؤلفون: Jana Neirinck, Annelies Emmaneel, Malicorne Buysse, Jan Philippé, Sofie Van Gassen, Yvan Saeys, Xavier Bossuyt, Stefanie De Buyser, Mirjam van der Burg, Martín Pérez-Andrés, Alberto Orfao, Jacques J. M. van Dongen, Bart N. Lambrecht, Tessa Kerre, Mattias Hofmans, Filomeen Haerynck, Carolien Bonroy
المصدر: Frontiers in Immunology, Vol 13 (2022)
مصطلحات موضوعية: flow cytometry, immunophenotyping analysis, EuroFlow standardization, clinical validation, primary immunodeficiencies (PID), Immunologic diseases. Allergy, RC581-607
الوصف: IntroductionMultiparameter flow cytometry (FCM) immunophenotyping is an important tool in the diagnostic screening and classification of primary immunodeficiencies (PIDs). The EuroFlow Consortium recently developed the PID Orientation Tube (PIDOT) as a universal screening tool to identify lymphoid-PID in suspicious patients. Although PIDOT can identify different lymphoid-PIDs with high sensitivity, clinical validation in a broad spectrum of patients with suspicion of PID is missing. In this study, we investigated the diagnostic performance of PIDOT, as part of the EuroFlow diagnostic screening algorithm for lymphoid-PID, in a daily practice at a tertiary reference center for PID.MethodsPIDOT was tested in 887 consecutive patients suspicious of PID at the Ghent University Hospital, Belgium. Patients were classified into distinct subgroups of lymphoid-PID vs. non-PID disease controls (non-PID DCs), according to the IUIS and ESID criteria. For the clinical validation of PIDOT, comprehensive characterization of the lymphoid defects was performed, together with the identification of the most discriminative cell subsets to distinguish lymphoid-PID from non-PID DCs. Next, a decision-tree algorithm was designed to guide subsequent FCM analyses.ResultsThe mean number of lymphoid defects detected by PIDOT in blood was 2.87 times higher in lymphoid-PID patients vs. non-PID DCs (p < 0.001), resulting in an overall sensitivity and specificity of 87% and 62% to detect severe combined immunodeficiency (SCID), combined immunodeficiency with associated or syndromic features (CID), immune dysregulation disorder (ID), and common variable immunodeficiency (CVID). The most discriminative populations were total memory and switched memory B cells, total T cells, TCD4+cells, and naive TCD4+cells, together with serum immunoglobulin levels. Based on these findings, a decision-tree algorithm was designed to guide further FCM analyses, which resulted in an overall sensitivity and specificity for all lymphoid-PIDs of 86% and 82%, respectively.ConclusionAltogether, our findings confirm that PIDOT is a powerful tool for the diagnostic screening of lymphoid-PID, particularly to discriminate (S)CID, ID, and CVID patients from other patients suspicious of PID. The combination of PIDOT and serum immunoglobulin levels provides an efficient guide for further immunophenotypic FCM analyses, complementary to functional and genetic assays, for accurate PID diagnostics.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.937738/fullTest; https://doaj.org/toc/1664-3224Test
-
9دورية أكاديمية
المؤلفون: Bram Decru, Jan Van Elslande, Sophie Steels, Gijs Van Pottelbergh, Lode Godderis, Bram Van Holm, Xavier Bossuyt, Johan Van Weyenbergh, Piet Maes, Pieter Vermeersch
المصدر: Frontiers in Immunology, Vol 13 (2022)
مصطلحات موضوعية: SARS-CoV-2, COVD-19 serological testing, neutralizing antibodies, vaccination, spike, IgG, Immunologic diseases. Allergy, RC581-607
الوصف: BackgroundIgG anti-spike (S) antibodies arise after SARS-CoV-2 infection as well as vaccination. Levels of IgG anti-S are linked to neutralizing antibody titers and protection against (re)infection.MethodsWe measured IgG anti-S and surrogate neutralizing antibody kinetics against Wild Type (WT) and 4 Variants of Concern (VOC) in health care workers (HCW) 3 and 10 months after natural infection (“infection”, n=83) or vaccination (2 doses of BNT162b2) with (“hybrid immunity”, n=17) or without prior SARS-CoV-2 infection (“vaccination”, n=97).ResultsThe humoral immune response in the “vaccination” cohort was higher at 3 months, but lower at 10 months, compared to the “infection” cohort due to a faster decline. The “hybrid immunity” cohort had the highest antibody levels at 3 and 10 months with a slower decline compared to the “vaccination” cohort. Surrogate neutralizing antibody levels (expressed as %inhibition of ACE-2 binding) showed a linear relation with log10 of IgG anti-S against WT and four VOC. IgG anti-S corresponding to 90% inhibition ranged from 489 BAU/mL for WT to 1756 BAU/mL for Beta variant. Broad pseudoneutralization predicted live virus neutralization of Omicron BA.1 in 20 randomly selected high titer samples.ConclusionsHybrid immunity resulted in the strongest humoral immune response. Antibodies induced by natural infection decreased more slowly than after vaccination, resulting in higher antibody levels at 10 months compared to vaccinated HCW without prior infection. There was a linear relationship between surrogate neutralizing activity and log10 IgG anti-S for WT and 4 VOC, although some VOC showed reduced sensitivity to pseudoneutralization.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.909910/fullTest; https://doaj.org/toc/1664-3224Test
-
10دورية أكاديمية
المؤلفون: Mariangela Manfredi, Lieve Van Hoovels, Maurizio Benucci, Riccardo De Luca, Carmela Coccia, Pamela Bernardini, Edda Russo, Amedeo Amedei, Serena Guiducci, Valentina Grossi, Xavier Bossuyt, Carlo Perricone, Maria Infantino
المصدر: Journal of Personalized Medicine, Vol 13, Iss 4, p 688 (2023)
مصطلحات موضوعية: suPAR, rheumatoid arthritis, autoimmune diseases, rheumatic diseases, Medicine
الوصف: The soluble urokinase plasminogen activator receptor (suPAR) is the bioactive form of uPAR, a membrane-bound glycoprotein, and it is primarily expressed on the surface of immunologically active cells. Mirroring local inflammation and immune activation, suPAR has gained interest as a potential prognostic biomarker in several inflammatory diseases. Indeed, in many diseases, including cancer, diabetes, cardiovascular diseases, kidney diseases, and inflammatory disorders, higher suPAR concentrations have been associated with disease severity, disease relapse, and mortality. Our review describes and discusses the supporting literature concerning the promising role of suPAR as a biomarker in different autoimmune rheumatic and non-rheumatic diseases.
وصف الملف: electronic resource
النص الكامل