Pre-treatment With Azithromycin to Reduce Immunogenicity to Anti-Tumor Necrosis Factor-α Agents in Patients With Inflammatory Bowel Disease
Ontology highlight
ABSTRACT:
DISEASE(S): Biological Substance; Adverse Effect,Inflammatory Bowel Diseases,Intestinal Diseases,Necrosis
PROVIDER: 2752894 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Background: The immunologic response to stress is regulated by the cytokines. Anti-Tumor Necrosis Factor-α agents are antibodies directed against a key cytokine in the process angiogenesis and collagen synthesis. It is not known whether they intervene with surgical stress response increasing the rate of postoperative complications.
Method: Un-blinded prospective, non-interventional cohort single centre study including all the patients with Crohn’s disease and Ulcerative Colitis undergoing abdominal surgery. Immunological and endocrinological parameters will measured in blood samples taken from these patients before and after surgery. Power calculations showed that 17 patients in each arm are needed.
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Project description:Anti-TNF (tumor necrosis factor) monoclonal antibodies have revolutionized management of Inflammatory bowel disease. Their common features include high efficacy but also immunogenicity and increased infection risk. Since 2013, two generics or biosimilars of the first anti-TNF have been registered in Europe, which long lerm safety profile needs yet to be established.
This prospective, multicenter, observational cohort study will assess safety of treatment of anti-TNF monoclonal antibodies in inflammatory bowel disease patients in Poland.
Eligible are consecutive patients in whom anti-TNF is started for Crohn’s disease, ulcerative colitis or indeterminate colitis between January 1st, 2014 and December 31st, 2015. Data to be collected include demography, Montreal classification, indication to treatment, previous treatment, operations, extraintestinal manifestations and concomitant diseases. Data on response, tolerability and safety of anti-TNF and on concomitant treatment will be collected. Adverse events logs will be completed. Majority of IBD centres in Poland, pediatric and adult, academic and regional, have agreed to participate in the study.
As a result of the study, the frequency of adverse events in a cohort of Polish IBD patients on various anti-TNFs will be established.
| 2161078 | ecrin-mdr-crc
Project description:Objectives: To investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna), and evaluate the impact of anti-rheumatic medications on immunogenicity in patients with autoimmune rheumatic diseases (AIRD). Methods: From September 16 to November 15, 2021, we consecutively enrolled participants aged≥20 years with AIRD who received COVID-19 vaccination. The level of serum IgG antibodies to the SARS-Cov-2 receptor-binding domain on the spike protein S1 subunit was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. The immunogenicity and adverse reactions between ChAdOx1 nCov-19/AZD1222 and mRNA-1273 were compared. Results: Of the 243 rheumatic disease patients who received COVID-19 vaccines, 113 and 130 were immunized with AZD1222 and mRNA-1273, respectively. The anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-Cov-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222. Prednisolone-equivalent dose >5 mg/day, methotrexate (MTX), non-anti-tumor necrosis factor (TNF)-a biologics, and Janus kinase (JAK) inhibitor use were associated with inferior immunogenicity. All reported adverse reactions were minor. More localized pain at the injection site and less fever and chills were observed in patients receiving mRNA-1273 compared with those receiving AZD1222. Rheumatic disease activities after vaccination remained stable in most patients. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity and adverse reaction profiles. Our study findings support temporary discontinuation of daily prednisolone dose >5 mg, MTX, non-anti-TNF-a biologics, or JAK inhibitors after COVID-19 vaccination.
2022-05-19 | GSE203081 | GEO
Project description:The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin. The genes modulated by TNF-alpha were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin increases expression of transcription factors that form part of the integrated stress response which is accompanied by reduced expression of genes involved in DNA repair. This study confirms that hemozoin induces cellular stress on erythroblasts that is additional to and distinct from responses to inflammatory cytokines and identifies new genes that may be involved in the pathogenesis of severe malarial anemia. More generally the respective transcription profiles highlight the varied mechanisms through which erythropoiesis may be disrupted during infectious disease. Erythroblasts derived from PBMCs were enriched to 97% purity for proerythroblast and intermediate/normoblast phases of differentiation using magnetic bead isolation. There were three treatment groups: media, P.falciparum hemozoin (12.5 microgram /ml hematin units) and tumour necrosis factor alpha(10ng/ml). Total RNA using 7.5 x105 cells per treatment from one donor was extracted using Trizol. Highly significant gene ontological findings (where p> x10^-17 but < x10^-7) were confirmed by quantitative PCR.
2015-02-04 | E-GEOD-65577 | biostudies-arrayexpress
Project description:Cellular functions of trophoblasts are regulated by various cytokines and growth factors. We previously reported the synergistic effects of tumor necrosis factor-α (TNF-α) and insulin-like growth factor-I (IGF-I) on BeWo cells proliferation. We performed DNA methylation array to elucidate the epigenetic regulation involved in the cross-talk of TNF-α and IGF-I in BeWo cells. We identified general increase in DNA methylation by co-stimulation of TNF-α and IGF-I. Total of 83474 differentially methylated CpG sites were identified in BeWo cells stimulated by IGF-I and high TNF-α. By correlating with the results of expression array, NFKBIE, C3 and GP1BA were identified as differentially methylated genes with significant expression change.
2019-12-10 | GSE119652 | GEO
Project description:To test the efficacy of TNFR-Fc and anti-TWEAK mAb treatment alone and in combination Tumor necrosis factor (TNF)-alpha is a major effector in various inflammatory conditions. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily that promotes inflammatory tissue damage through its receptor, FGF-inducible molecule 14 (Fn14). Since both TWEAK and TNF-alpha have been shown to mediate pathological responses through inter-dependent or independent pathways by in vitro, the potential interplay of these pathways was investigated in a mouse colitis model. Acute colitis was induced by rectal injection of trinitrobenzene sulfonic acid (TNBS), with administration of control IgG, TNF receptor (TNFR)-Ig chimeric protein, anti-TWEAK monoclonal antibody, or the combination of TNFR-Ig and anti-TWEAK antibody. On day 4, disease severity was evaluated and gene expression profiling was analyzed using whole colon tissue. Levels of transcript of TWEAK, Fn14 and NF-kB-related molecules were measured in purified colon epithelial cells (ECs). NF-kB activation was investigated with Western blot and immunohistochemical analysis. As a result, activation of the canonical, but not noncanonical NF-kB pathway was the hallmark of inflammatory responses in this model. Inflammation induced upregulation of Fn14 only in ECs but not in other cell types. Combination treatment of TNFR-Ig and anti-TWEAK antibody synergistically reduced disease severity in comparison with the control antibody or single agent treatment. Gene expression profile of the colon indicated downregulation of canonical NF-kB pathway with combination treatment. In conclusion, synergistic activation of canonical NF-kB by TWEAK and TNF-alpha is critical for the induction of inflammatory tissue damage in acute inflammation.
2014-05-30 | GSE53835 | GEO
Project description:Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract. We performed a whole-genome transcriptional analysis using colonic biopsies from CD patients before and after anti-TNF-α therapy. Involved colonic samples from Crohn's disease patients and healthy colonic samples from non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for CD patients were: age between 18 and 70, diagnosis of CD established at least 4 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and clinical score: endoscopic active disease was defined as a CD endoscopic index of severity (CDEIS) of 5 or more and the presence of large ulcers (> 0.5 cm diameter) in at least one of the explored segments. Clinical activity was defined as a CD activity index (CDAI) above 150. Finally, a total of 39 biopsies were analyzed: 17 healthy controls, 10 active CD without anti-TNF therapy, 5 active CD with anti-TNF therapy (non-responders) and 7 inactive CD with anti-TNF therapy (responders).
2014-04-08 | E-GEOD-52746 | biostudies-arrayexpress
Project description:Metabolic signature of HepaRG cells exposed to ethanol and tumor necrosis factor alpha to study ethanol-induced hepatotoxicity by LC-MS-based untargeted metabolomics.
Dataset contains .mzML files originating from an LC-QTOF (6530 for metabolomics & 6560 for lipidomics). HepaRG samples were exposed to ethanol, ethanol & TNF-alpha or no ethanol and TNF-alpha (i.e. negative control). In addition, data from extraction blanks and QC pooled samples are available. Both intracellular and extracellular extracts were analyzed on four different platforms (metabolomics in ESI+ and ESI- and lipidomics in ESI+ and ESI-).
2022-11-23 | MSV000090773 | MassIVE
Project description:Cellular functions of trophoblasts are regulated by various cytokines and growth factors. We previously reported the synergistic effects of tumor necrosis factor-α (TNF-α) and insulin-like growth factor-I (IGF-I) on BeWo cells proliferation. We performed gene expression array to elucidate the genes involved in the cross-talk of TNF-α and IGF-I in BeWo cells. We identified 553 differentially expressed genes (DEGs) under the co-stimulation of TNF-α and IGF-I. Gene ontology analysis identified “NF-kappa B signaling pathway”, “Calcium signaling pathway”, and “Arachidonic acid metabolism”. Among DEGs, PTGS2 was up-regulated and PTGER2 was down-regulated.
2019-12-10 | GSE119651 | GEO
Project description:To test the efficacy of TNFR-Fc and anti-TWEAK mAb treatment alone and in combination Tumor necrosis factor (TNF)-alpha is a major effector in various inflammatory conditions. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily that promotes inflammatory tissue damage through its receptor, FGF-inducible molecule 14 (Fn14). Since both TWEAK and TNF-alpha have been shown to mediate pathological responses through inter-dependent or independent pathways by in vitro, the potential interplay of these pathways was investigated in a mouse colitis model. Acute colitis was induced by rectal injection of trinitrobenzene sulfonic acid (TNBS), with administration of control IgG, TNF receptor (TNFR)-Ig chimeric protein, anti-TWEAK monoclonal antibody, or the combination of TNFR-Ig and anti-TWEAK antibody. On day 4, disease severity was evaluated and gene expression profiling was analyzed using whole colon tissue. Levels of transcript of TWEAK, Fn14 and NF-kB-related molecules were measured in purified colon epithelial cells (ECs). NF-kB activation was investigated with Western blot and immunohistochemical analysis. As a result, activation of the canonical, but not noncanonical NF-kB pathway was the hallmark of inflammatory responses in this model. Inflammation induced upregulation of Fn14 only in ECs but not in other cell types. Combination treatment of TNFR-Ig and anti-TWEAK antibody synergistically reduced disease severity in comparison with the control antibody or single agent treatment. Gene expression profile of the colon indicated downregulation of canonical NF-kB pathway with combination treatment. In conclusion, synergistic activation of canonical NF-kB by TWEAK and TNF-alpha is critical for the induction of inflammatory tissue damage in acute inflammation. TNBS colitis was induced by intrarectal administration of a 2 % solution of TNBS in phosphate-buffered saline (PBS): ethanol (1:1). For acute inflammatory responses, 70 M-NM-<g/g body weight of TNBS was given on day 0 and animals sacrificed on day 4. One hour prior to administration of TNBS, groups of mice were injected i.p. with the control IgG2a mAb (anti-human CD20) (10 mg/kg), TNFR-Ig (0.3 mg/kg), anti-TWEAK (mP2D10, 10 mg/kg), the combination of TNFR-Fc (0.3 mg/kg) and anti-TWEAK mP2D10 (10 mg/kg), or were untreated. For single agent and combination treatments groups, 0.3 mg/kg TNFR-Ig was employed, since 1 mg/kg of TNFR-Ig markedly ameliorated TNBS colitis but 0.3 mg/kg was much less effective as monitored by the effect on colon length and body weight. Colon tissue was rolled and snap-frozen in liquid nitrogen. Specimens for RNA extraction were cut from the frozen rolled colon. A set of experiments using 5-8 mice for each experimental group was performed twice, labelled 7 and 10 in the CEL files. Total number of mice for each experimental condition was as follows; untreated TNBS colitis group, 8; control antibody, 15; TNFR-Ig, 12; anti-TWEAK mAb, 14; combination of TNFR-Ig and anti-TWEAK mAb, 15.
2014-05-30 | E-GEOD-53835 | biostudies-arrayexpress