18 results on '"Arts, Rob J."'
Search Results
2. OTULIN Haploinsufficiency-Related Fasciitis and Skin Necrosis Treated by TNF Inhibition
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MMB Onderzoek en Onderwijs, Infection & Immunity, MMB Medische Staf, Arts, Rob J W, van der Linden, Tristan J, van der Made, Caspar I, Hendriks, Marianne M C, van der Heijden, Wouter A, de Mast, Quirijn, Schuurs-Hoeijmakers, Janneke H M, Simons, Annet, Spaan, András N, Mulders-Manders, Catharina M, van de Veerdonk, Frank L, MMB Onderzoek en Onderwijs, Infection & Immunity, MMB Medische Staf, Arts, Rob J W, van der Linden, Tristan J, van der Made, Caspar I, Hendriks, Marianne M C, van der Heijden, Wouter A, de Mast, Quirijn, Schuurs-Hoeijmakers, Janneke H M, Simons, Annet, Spaan, András N, Mulders-Manders, Catharina M, and van de Veerdonk, Frank L
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- 2024
3. OTULIN Haploinsufficiency-Related Fasciitis and Skin Necrosis Treated by TNF Inhibition
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Arts, Rob J. W., primary, van der Linden, Tristan J., additional, van der Made, Caspar I., additional, Hendriks, Marianne M. C., additional, van der Heijden, Wouter A., additional, de Mast, Quirijn, additional, Schuurs-Hoeijmakers, Janneke H. M., additional, Simons, Annet, additional, Spaan, András N., additional, Mulders-Manders, Catharina M., additional, and van de Veerdonk, Frank L., additional
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- 2023
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4. Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings.
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van Geuns, Dorine, Arts, Rob J. W., de Vries, Gerard, Wit, Ferdinand W. N. M., Degtyareva, Svetlana Y., Brown, James, Pareek, Manish, Lipman, Marc, and van Crevel, Reinout
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- 2024
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5. Anticytokine Autoantibodies in Infectious Diseases: A Practical Overview.
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Arts, Rob J. W., Janssen, Nico A. F., and van de Veerdonk, Frank L.
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AUTOANTIBODIES , *COMMUNICABLE diseases , *IMMUNOSPECIFICITY , *AUTOIMMUNITY , *IMMUNOGLOBULINS , *FC receptors - Abstract
Anticytokine autoantibodies (ACAAs) are a fascinating group of antibodies that have gained more and more attention in the field of autoimmunity and secondary immunodeficiencies over the years. Some of these antibodies are characterized by their ability to target and neutralize specific cytokines. ACAAs can play a role in the susceptibility to several infectious diseases, and their infectious manifestations depending on which specific immunological pathway is affected. In this review, we will give an outline per infection in which ACAAs might play a role and whether additional immunomodulatory treatment next to antimicrobial treatment can be considered. Finally, we describe the areas for future research on ACAAs. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Opposing Effects of Interleukin-36γ and Interleukin-38 on Trained Immunity
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Teufel, Lisa U., primary, Netea, Mihai G., additional, van de Veerdonk, Frank L., additional, Dinarello, Charles A., additional, Joosten, Leo A. B., additional, and Arts, Rob J. W., additional
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- 2023
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7. Circulating interleukin-38 concentrations in healthy adults
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Teufel, Lisa U., primary, de Graaf, Dennis M., additional, Netea, Mihai G., additional, Dinarello, Charles A., additional, Joosten, Leo A. B., additional, and Arts, Rob J. W., additional
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- 2022
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8. Exploratory analysis of interleukin‐38 in hospitalized COVID‐19 patients.
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de Graaf, Dennis M., Teufel, Lisa U., de Nooijer, Aline H., van Gammeren, Adriaan J., Ermens, Antonius A. M., Gaál, Ildikó O., Crișan, Tania O., van de Veerdonk, Frank L., Netea, Mihai G., Dinarello, Charles A., Joosten, Leo A. B., and Arts, Rob J. W.
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COVID-19 ,HOSPITAL patients ,VIRUS diseases ,EXTRACELLULAR matrix proteins ,IMMUNOGLOBULIN receptors - Abstract
Introduction: A major contributor to coronavirus disease 2019 (COVID‐19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin‐38 (IL−38) is an IL‐1 family member with broad anti‐inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL‐38 in COVID‐19 patients in comparison to healthy controls, whereas two other studies report no differences in IL‐38 concentrations. Methods: Here, we present an exploratory, retrospective cohort study of circulating IL‐38 concentrations in hospitalized COVID‐19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age‐ and sex‐matched healthy subjects. Plasma IL‐38 concentrations were measured by enzyme‐linked immunosorbent assay, disease‐related proteins by proximity extension assay, and clinical data were retrieved from hospital records. Results: IL‐38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL‐38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL‐38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL‐38 and the inflammatory biomarker d‐dimer was observed in men of the validation cohort. In women of the validation cohort, IL‐38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL‐38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL‐10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein. Conclusions: These data indicate that IL‐38 is not associated with disease outcomes in hospitalized COVID‐19 patients. However, moderate correlations between IL‐38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL‐38 concentrations are not indicative of COVID‐19 severity, its anti‐inflammatory effects may reduce COVID‐19 severity and should be experimentally investigated. [ABSTRACT FROM AUTHOR]
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- 2022
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9. IL‐38 prevents induction of trained immunity by inhibition of mTOR signaling.
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de Graaf, Dennis M., Teufel, Lisa U., van de Veerdonk, Frank L., Joosten, Leo A. B., Netea, Mihai G., Dinarello, Charles A., and Arts, Rob J. W.
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BETA-glucans ,BONE marrow cells ,LABORATORY mice ,SINGLE nucleotide polymorphisms ,IMMUNITY ,PHENOTYPES - Abstract
Trained immunity is the acquisition of a hyperresponsive phenotype by innate immune cells (such as monocytes and macrophages) after an infection or vaccination, a de facto nonspecific memory dependent on epigenetic and metabolic reprogramming of these cells. We have recently shown that induction of trained immunity is dependent on IL‐1β. Here, we show that recombinant IL‐38, an anti‐inflammatory cytokine of the IL‐1‐family, was able to induce long‐term inhibitory changes and reduce the induction of trained immunity by β‐glucan in vivo in C57BL/6 mice and ex vivo in their bone marrow cells. IL‐38 blocked mTOR signaling and prevented the epigenetic and metabolic changes induced by β‐glucan. In healthy subjects, the IL1F10 associated single nucleotide polymorphism rs58965312 correlated with higher plasma IL‐38 concentrations and reduced induction of trained immunity by β‐glucan ex vivo. These results indicate that IL‐38 induces long‐term anti‐inflammatory changes and also inhibits the induction of trained immunity. Recombinant IL‐38 could therefore potentially be used as a therapeutic intervention for diseases characterized by exacerbated trained immunity. [ABSTRACT FROM AUTHOR]
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- 2021
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10. IL‐38 prevents induction of trained immunity by inhibition of mTOR signaling
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Graaf, Dennis M., Teufel, Lisa U., Veerdonk, Frank L., Joosten, Leo A. B., Netea, Mihai G., Dinarello, Charles A., and Arts, Rob J. W.
- Abstract
Trained immunity is the acquisition of a hyperresponsive phenotype by innate immune cells (such as monocytes and macrophages) after an infection or vaccination, a de factononspecific memory dependent on epigenetic and metabolic reprogramming of these cells. We have recently shown that induction of trained immunity is dependent on IL‐1β. Here, we show that recombinant IL‐38, an anti‐inflammatory cytokine of the IL‐1‐family, was able to induce long‐term inhibitory changes and reduce the induction of trained immunity by β‐glucan in vivo in C57BL/6 mice and ex vivoin their bone marrow cells. IL‐38 blocked mTOR signaling and prevented the epigenetic and metabolic changes induced by β‐glucan. In healthy subjects, the IL1F10associated single nucleotide polymorphism rs58965312 correlated with higher plasma IL‐38 concentrations and reduced induction of trained immunity by β‐glucan ex vivo. These results indicate that IL‐38 induces long‐term anti‐inflammatory changes and also inhibits the induction of trained immunity. Recombinant IL‐38 could therefore potentially be used as a therapeutic intervention for diseases characterized by exacerbated trained immunity. IL‐38 inhibits the induction of innate immune memory
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- 2021
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11. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease
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Molteni, Raffaella, Biavasco, Riccardo, Stefanoni, Davide, Nemkov, Travis, Domínguez-Andrés, Jorge, Arts, Rob J., Merelli, Ivan, Mazza, Davide, Zambrano, Samuel, Panigada, Maddalena, Cantoni, Eleonora, Tengesdal, Isak W., Maksud, Philippe, Piras, Francesco, Cesana, Daniela, Cassina, Laura, Distefano, Gianfranco, Loffreda, Alessia, Gnani, Daniela, De Luca, Giacomo, Tomelleri, Alessandro, Campochiaro, Corrado, Joosten, Leo A.B., Dinarello, Charles A., Kajaste-Rudnitski, Anna, Haroche, Julien, Cardaci, Simone, Cenci, Simone, Dagna, Lorenzo, Doglioni, Claudio, Ferrarini, Marina, Ferrero, Elisabetta, Boletta, Alessandra, D'Alessandro, Angelo, Montini, Eugenio, Netea, Mihai G., and Cavalli, Giulio
- Abstract
Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.
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- 2021
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12. Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis.
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Vorsteveld EE, Van der Made CI, Smeekens SP, Schuurs-Hoeijmakers JH, Astuti G, Diepstra H, Gilissen C, Hoenselaar E, Janssen A, van Roozendaal K, Engelen JS, Steyaert W, Weiss MM, Yntema HG, Mantere T, AlZahrani MS, van Aerde K, Derfalvi B, Faqeih EA, Henriet SSV, van Hoof E, Idressi E, Issekutz TB, Jongmans MCJ, Keski-Filppula R, Krapels I, Te Loo M, Mulders-Manders CM, Ten Oever J, Potjewijd J, Sarhan NT, Slot MC, Terhal PA, Thijs H, Vandersteen A, Vanhoutte EK, van de Veerdonk F, van Well G, Netea MG, Simons A, Hoischen A, Arts RJW, Bijker EM, Bruno M, Hobo W, Hoppenreijs E, de Jonge MI, van Laarhoven A, van der Molen R, Oud M, Schatorje EJH, Smeets R, Sprenkeler EGG, Stol K, Verhagen LM, and Zonneveld-Huijssoon E
- Abstract
While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8 %. Through systematic reanalysis, we identified variants of interest in 5.2 % of undiagnosed patients, with 76.7 % being (candidate) disease-causing, providing a (candidate) diagnosis in 15.2 % of our cohort. We find a 1.7 percentage point increase in conclusive molecular diagnoses. We find a high degree of actionability in patients with a genetic diagnosis (76.4 %). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in IEI patients, conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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13. Interleukin 38 reduces antigen-presentation capacity and antibody production after vaccination.
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Teufel LU, Taks EJM, van Gemert J, Neacsu M, Föhse K, Gillard J, Diavatopoulos DA, de Jonge MI, Netea MG, Joosten LAB, and Arts RJW
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The mechanisms that underpin low vaccine responses, which can lead to inadequate protection against infection, are still partially unclear. Interleukin (IL)-38 is a member of the IL-1 family, expressed by B cells among others, that regulates inflammatory responses. A recent study shows that IL-38 suppresses plasma cell generation and antibody production upon immune activation. We hypothesis that IL-38 affects antigen-presentation capacity of innate immune cells, effecting antibody production. Here, we investigated the effect of recombinant human IL-38 on human peripheral blood mononuclear cells and myeloid-derived DCs regarding cytokine production, phagocytosis, and expression of MCH II and co-stimulatory proteins in vitro, and further relate circulating plasma IL-38 concentrations to antibody responses in a cohort of 75 females aged 18-48 vaccinated with BCG and Tdap-IPV. To this end, we found that IL-38 decreased the expression of HLA-DR, HLA-DM, and CD83 on PBMCs, and CD40 and CD86 on MDDCs. IL-38 further impaired phagocytosis capacity of monocytes. Lastly, antibody production against diphtheria toxoids up to eight months post-vaccination was negatively associated with IL-38 plasma concentrations. These data suggest that IL-38 could dampen the effectiveness of antigen-presentation and phagocytosis, and could therefore modulate the immunogenicity of some vaccine types., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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14. Insights into the multifaceted role of interleukin-37 on human immune cell regulation.
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Teufel LU, Matzaraki V, Folkman L, Ter Horst R, Moorlag SJCFM, Mulders-Manders CM, Netea MG, Krausgruber T, Joosten LAB, and Arts RJW
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Autoinflammatory diseases, while having a variety of underlying causes, are mediated by dysfunctional innate immune responses. Therefore, standard treatments target innate cytokines or block their receptors. Despite excellent responses in some patients, first-line treatments fail in others, for reasons which remain to be understood. We studied the effects of IL-37, an anti-inflammatory cytokine, on immune cells using multi-omics profiling of 325 healthy adults. Our findings show that IL-37 is associated with inflammation control and generally reduced immune cell activity. Further, genetic variants in IL37 are associated with impaired trained immunity, a memory phenotype of innate immune cells contributing to autoinflammation. To underpin the medical potential of IL-37, an explorative cohort of seven autoinflammatory disorders was built. In vitro stimulation experiments argue for recombinant IL-37 as a potential therapy in IL-6-, and IL-22-driven conditions. Concluding, IL-37 is highlighted as a cytokine with broad anti-inflammatory functions, implicating its potential as therapeutic intervention., Competing Interests: Declaration of competing interest M.G.N. and L.A.B.J. are scientific founders of Trained Therapeutix and Discovery (TTxD), Lemba TX and Salvina TX., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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15. Anticytokine Autoantibodies in Infectious Diseases: A Practical Overview.
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Arts RJW, Janssen NAF, and van de Veerdonk FL
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- Humans, Autoimmunity, Cytokines, Immunomodulation, Autoantibodies, Communicable Diseases
- Abstract
Anticytokine autoantibodies (ACAAs) are a fascinating group of antibodies that have gained more and more attention in the field of autoimmunity and secondary immunodeficiencies over the years. Some of these antibodies are characterized by their ability to target and neutralize specific cytokines. ACAAs can play a role in the susceptibility to several infectious diseases, and their infectious manifestations depending on which specific immunological pathway is affected. In this review, we will give an outline per infection in which ACAAs might play a role and whether additional immunomodulatory treatment next to antimicrobial treatment can be considered. Finally, we describe the areas for future research on ACAAs.
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- 2023
- Full Text
- View/download PDF
16. A difficult to treat Leishmania infantum relapse after allogeneic stem cell transplantation.
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Arts RJW, Ector GICG, Bosch-Nicolau P, Molina I, McCall MBB, van der Velden WJFM, van Laarhoven A, de Mast Q, and van Dorp S
- Abstract
Here we describe a complicated case of a relapsed Leishmania infantum infection after an allogeneic stem cell transplantation (allo-SCT) for primary myelofibrosis. Three years earlier the patient had been diagnosed with a hemophagocytic lymphohistiocytosis secondary to a visceral Leishmania infantum infection, for which he was effectively treated with a cumulative dose of 40 mg/kg liposomal amphotericin B. During the first disease episode he was also diagnosed with primary myelofibrosis for which he received medical follow-up. One year later ruxolitinib was started due to progressive disease. No Leishmania relapse occurred. Nevertheless, the marrow fibrosis progressed, and an allo-SCT was performed. Two months after allo-SCT prolonged fever and a persistent pancytopenia occurred, which was due to a relapse of visceral Leishmaniasis. The infection was refractory to a prolonged treatment with liposomal amphotericin B with a cumulative dose up to 100 mg/kg. Salvage treatment with miltefosine led to reduction of fever within a few days and was followed by a slow recovery of pancytopenia over the following months. The Leishmania parasite load by PCR started to decline and after 3.5 months no Leishmania DNA could be detected anymore and follow-up until ten months afterwards did not show a relapse., Competing Interests: None., (© 2023 The Authors.)
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- 2023
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17. Effect of exogenous IL-37 on immune cells from a patient carrying a potential IL37 loss-of-function variant: A case study.
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Teufel LU, van der Made CI, Klück V, Simons A, Hoischen A, Vernimmen V, Joosten LAB, and Arts RJW
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- Humans, Cytokines genetics, Inflammation, Gene Expression, Interleukin-1 metabolism, Interleukin-17 genetics
- Abstract
Introduction: Chronic inflammatory or autoimmune diseases are commonly treated with immunosuppressive medication such as NSAIDs, corticosteroids, or antibodies against specific cytokines (TNF, IL-1 IL-17, IL-23, etc.) or signalling cascades (e.g. JAK-STAT inhibitors). Using sequencing data to locate genetic mutations in relevant genes allows the identification of alternative targets in a patient-tailored therapy setting. Interleukin (IL)-37 is an anti-inflammatory cytokine with broad effects on innate and adaptive immune cell function. Dysfunctional IL-37 expression or signalling is linked to various autoinflammatory disorders. The administration of recombinant IL-37 to hyperinflammatory patients that are non-responsive to standard treatment bears the potential to alleviate symptoms., Methods: In this case study, the (hyper)responsiveness of immune cell subsets was investigated in a single patient with a seronegative autoimmune disorder who carries a heterozygous stop-gain variant in IL37 (IL37 Chr2(GRCh37):g.113670640G > A NM_014439.3:c.51G > A p.(Trp17*)). As the patient has been non-responsive to blockage of TNF or IL-1 by Etanercept or Anakinra, respectively, additional in-vitro experiments were set out to elucidate whether treatment with recombinant IL-37 could normalise observed immune cell functions., Findings: Characterisation of immune cell function showed no elevated overall production of acute-phase pro-inflammatory cytokines by patient PBMCs and neutrophils at baseline or upon stimulation. T-cell responses were elevated, as was the metabolic activity and IL-1Ra production of PBMCs at baseline. The identified stop-gain variant in IL37 does not result in the absence of the protein in circulation. In line with this, treatment with recombinant IL-37 did overall not dampen immune responses with the exception of the complete suppression of IL-17., Conclusion: The heterozygous stop-gain variant in IL37 (IL37 NM_014439.3:c.51G > A p.(Trp17*)) is not of functional relevance as we observed no clear pro-inflammatory phenotype in immune cells of a patient carrying this variant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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18. IL-1 family cytokines as drivers and inhibitors of trained immunity.
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Teufel LU, Arts RJW, Netea MG, Dinarello CA, and Joosten LAB
- Subjects
- Cells, Cultured, Interleukin-1, Cytokines, Immunity, Innate
- Abstract
Trained immunity is the long-term memory of innate immune cells, characterised by increased pro-inflammatory responses towards homo- and heterologous secondary stimuli. Interleukin (IL)-1 signalling plays an essential role in the induction of trained immunity, also called innate immune memory. As such, certain anti-inflammatory members of the IL-1 family of cytokines (IL-1F) which interfere with the inflammatory process have the potential to regulate the induction of a trained phenotype. The aim of this review is to provide an update on the role of IL-1F members in the context of trained immunity, emphasising the role of anti-inflammatory cytokines from the IL-1F to inhibit the induction of trained immunity, and touching upon their potential as therapeutics in IL-1-driven inflammatory disorders., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
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