Functional Relevance of Soluble TNF-α, Transmembrane TNF-α and TNF-Signal Transduction in Gastrointestinal Diseases with Special Reference to Inflammatory Bowel Diseases

2002 ◽  
Vol 40 (8) ◽  
pp. 587-600 ◽  
Author(s):  
M H Holtmann ◽  
M Schütz ◽  
P R Galle ◽  
M F Neurath
Keyword(s):  
Signal Transduction ◽  
Special Reference ◽  
Inflammatory Bowel Diseases ◽  
Gastrointestinal Diseases ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Functional Relevance

Anti-TNF-α agents and serum lipids in inflammatory bowel diseases

2016 ◽  
Vol 40 (4) ◽  
pp. e46-e47
Author(s):  
Çağdaş Kalkan ◽  
Fatih Karakaya ◽  
Murat Törüner ◽  
Hülya Çetinkaya ◽  
Irfan Soykan
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Serum Lipids ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells

2013 ◽  
Vol 304 (11) ◽  
pp. G970-G979 ◽  
Author(s):  
Andreas Fischer ◽  
Markus Gluth ◽  
Ulrich-Frank Pape ◽  
Bertram Wiedenmann ◽  
Franz Theuring ◽  
...  
Keyword(s):  
Tight Junction ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Model Systems ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Junction Proteins

Intestinal barrier dysfunction is pivotal in the etiology of inflammatory bowel diseases. Combined clinical and endoscopic remission (“mucosal healing”) in patients who received anti-TNF-α therapies suggests restitution of the intestinal barrier, but the mechanisms involved are largely unknown. We therefore investigated the impact of the anti-TNF-α antibody adalimumab on barrier function in two in vitro models. Combined stimulation of Caco-2 and T-84 cells with interferon-γ and TNF-α resulted in a significant decrease of transepithelial electrical resistance (TEER) within 6 h that was prevented by adalimumab in concentrations down to 100 ng/ml. Adalimumab furthermore antagonized the appearance of irregular membrane undulations and prevented internalization of tight junction proteins upon cytokine exposure. In addition, TNF-α induced a downregulation of claudin-1, claudin-2, claudin-4, and occludin as well as activation of phosphatidylinositol 3-kinase signaling in T-84 but not Caco-2 cells, which was reversed by adalimumab. At the signaling level, adalimumab prevented increased phosphorylation of myosin light chain as well as activation of p38 MAPK and NF-κB accompanying the decline in TEER in both model systems. Pharmacological inhibition of NF-κB signaling partially prevented the TNF-α-induced TEER loss, whereas inhibition of p38 worsened barrier dysfunction in Caco-2 but not T-84 cells. Taken together, these data demonstrate that adalimumab prevents barrier dysfunction induced by TNF-α both functionally and structurally as well as at the level of signal transduction. Barrier protection might therefore constitute a novel mechanism how anti-TNF-α therapy contributes to epithelial restitution and tissue repair in inflammatory bowel diseases.

Pregnancy and newborn outcome of mothers with inflammatory bowel diseases exposed to anti-TNF-α therapy during pregnancy: three-center study

2013 ◽  
Vol 48 (8) ◽  
pp. 951-958 ◽  
Author(s):  
Martin Bortlik ◽  
Nadezda Machkova ◽  
Dana Duricova ◽  
Karin Malickova ◽  
Ludek Hrdlicka ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Center Study

scholarly journals IMPORTANCE OF MEASURING LEVELS OF INFLIXIMAB IN PATIENTS TREATING INFLAMMATORY BOWEL DISEASE IN A BRAZILIAN COHORT

2017 ◽  
Vol 54 (4) ◽  
pp. 333-337 ◽  
Author(s):  
Katia Cristina KAMPA ◽  
Daphne Benatti Gonçalves MORSOLETTO ◽  
Marcela Rocha LOURES ◽  
Alcindo PISSAIA JUNIOR ◽  
Rodrigo Bremer NONES ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Clinical Symptoms ◽  
Serum Levels ◽  
Induction Phase ◽  
Tnf Α ◽  
Measurement Results ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Necrosis Factor ◽  
Chronic Inflammatory Bowel

ABSTRACT BACKGROUND: Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug’s effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. OBJECTIVE: This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. METHODS: It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. RESULTS: Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. CONCLUSION: In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing biologic therapy.

The role of PARK7 in the IL-17/TNF-α signaling pathway in pediatric inflammatory bowel diseases

Pancreatology ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. S120
Author(s):  
Rita Lippai ◽  
Erna Sziksz ◽  
Domonkos Pap ◽  
Réka Rokonay ◽  
Apor Veres-Székely ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Bowel Diseases ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals AB0484 TROUGH LEVELS OF TNF-Α INHIBITORS AND THEIR IMMUNOGENICITY IN THE TREATMENT OF RHEUMATIC DISEASES AND INFLAMMATORY BOWEL DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1269.2-1270
Author(s):  
T. Nuriakhmetova ◽  
I. K. Valeeva ◽  
J. Shevnina ◽  
D. Abdulganieva
Keyword(s):  
Rheumatic Diseases ◽  
Inflammatory Bowel Diseases ◽  
Trough Level ◽  
Certolizumab Pegol ◽  
Factors Associated ◽  
Low Level ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Trough Levels

Background:The features of the underlying immune-mediated disease can affect the efficacy, pharmacokinetics and immunogenicity of the biologic agents, which are among the important predictors of loss of response to TNF-α inhibitors (TNFi).Objectives:To compare the frequency of TNFi low trough levels and their immunogenicity in the treatment of rheumatic diseases (RD) (ankylosing spondylitis (AS) and rheumatoid arthritis (RA)) and inflammatory bowel diseases (IBD) (Crohn’s disease (CD) and ulcerative colitis (UC)).Methods:Among 120 patients (40 with AS (33.3%), 19 with RA (15.8%), 42 with CD (35%), and 19 with UC (15.8%)), trough level of infliximab (INX) (n=36, 30%), adalimumab (ADM) (n=45, 37.5%) and certolizumab pegol (CZP) (n=39, 32.5%) and the level of anti-drug antibodies (ADAb) were measured in the serum samples drawn directly before the planned drug administration.Results:Low drug level (below 0.5 μg/mL for INX1, 4.9 µg/ml for ADM2, and 20 µg/l for CZP3) was found in 54 (45%) patients: in 33 (55.9%) patients with RD and 21 (34.4%) patients with IBD. In the RD group, low drug trough level was observed more often than in IBD (55.9% vs 34.4%, OR 2.418, 95% CI 1.157 to 5.052, p=0.018). Only in UC was there a relationship between the received low dose of the drug (up to 200 mg of INX, 40 mg of ADM, and 200 mg of CZP) and its low level in the serum (p=0.026). Among the additional factors associated with a low TNFi level, lower dose of concomitant therapy at the time of a biologic initiation (66.7% vs 20.8%, OR 7.6, 95% CI 1.388 to 41.617, p=0.033) and the absence of pseudopolyps (78.9% vs 21.1%, p=0.045) were found in IBD, and in case of RD these factors included the age of 30 to 45 years (72.7% vs 41.9%, OR 3.692, 95 % CI 1.136 to 12.0, p=0.026), the absence of comorbidities (58.6% vs 41.4%, OR 3.44, 1.09 to 10.858, p=0.032) and male gender (78.8% vs 50% in women, OR 3.714, 95% CI 1.194 to 11.552, p=0.02).ADAb were detected in 29 (24.2%) patients (7 to INX (19.4%), 8 (17.8%) to ADM, 14 (35.9%) to CZP), 23 (79.3%) of which had also a concomitant low trough level of the drug. There were no significant differences in the frequency of ADAb formation between the pathologies. In the AS group, antibodies to CZP were detected in all patients with a low level of the biologic, while only in 25% of patients receiving ADM, a low level was associated with the formation of ADAb (p=0.019). In addition, among patients with AS, ADAb were detected only in those patients who did not take prednisone at the time of blood serum sampling (100% vs 37.9%, p=0.037).Conclusion:Low level of TNFi is more common in RD than in IBD. For each group, the factors associated with a low trough level of TNFi were identified. There were no significant differences in the frequency of ADAb formation between nosologies.References:[1]Steenholdt C, Bendtzen K, Brynskov J, et al. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scand J Gastroenterol 2011; 46: 310–318.[2]Bartelds GM, Krieckaert CL, Nurmohamed MT, van Schouwenburg PA, Lems WF, Twisk JW, Dijkmans BA, Aarden L, Wolbink GJ. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305:1460–1468. doi: 10.1001/jama.2011.406.[3]Gehin, J.E., Goll, G.L., Warren, D.J. et al. Associations between certolizumab pegol serum levels, anti-drug antibodies and treatment response in patients with inflammatory joint diseases: data from the NOR-DMARD study. Arthritis Res Ther 21, 256 (2019). https://doi.org/10.1186/s13075-019-2009-5Disclosure of Interests:Tatiana Nuriakhmetova Grant/research support from: A grant to purchase reagents for scientific research from Novartis Pharmaceuticals, Ildariya Khairullovna Valeeva: None declared., Jana Shevnina: None declared., Diana Abdulganieva: None declared.

Exploring pharmacogenetic variants for predicting response to anti-TNF therapy in autoimmune diseases: a meta-analysis

2021 ◽  
Author(s):  
Charalabos Antonatos ◽  
Eleana F Stavrou ◽  
Evangelos Evangelou ◽  
Yiannis Vasilopoulos
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Inflammatory Bowel Diseases ◽  
Meta Analysis ◽  
European Descent ◽  
Systematic Overview ◽  
Tnf Α ◽  
Subgroup Analyses ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Aim: The aim of this study is to explore how SNPs may affect the response to anti-TNF-α therapy in the major autoimmune diseases, such as psoriasis, rheumatoid arthritis, inflammatory bowel diseases and Spondyloarthritis. Methodology: We conducted a systematic overview on the field, by assessing all studies that examined the association between polymorphisms and response to anti-TNF-α therapy in participants of European descent. Results: In total, six independent SNPs located in FCGR2A, FCGR3A, TNF-α and TNFRSF1B genes were significantly associated with response to TNF-α blockers, found mainly in disease-subgroup analyses. Conclusion: No common pharmacogenetic variant was identified for all autoimmune diseases under study, suggesting the requirement of more studies in the field in order to capture such predictive variants that will aid treatment selection.

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