scholarly journals Decreased Immune Response to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases Treated with Anti TNFα

2021 ◽  
Author(s):  
Hadar Edelman-Klapper ◽  
Eran Zittan ◽  
Ariella Bar-Gil Shitrit ◽  
Keren Masha Rabinowitz ◽  
Idan Goren ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Bowel Diseases ◽  
Vaccine Dose ◽  
Drug Levels ◽  
Vaccine Responses ◽  
Tnf Α ◽  
Vaccine Booster ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Administration Timing

Background: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear. Aim: to assess immune responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC). Methods: Prospective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike (S) antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly. Results: Overall 258 subjects: 185 IBD (67 treated with anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while some patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-S levels were significantly lower in anti-TNFα treated compared to untreated patients, and HC (p<0.001; p<0.001, respectively). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared to untreated patients, and HC (p<0.03; p<0.0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-S levels. Infection rate (~2%) and AEs were comparable in all groups. IBD activity did not change in response to BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment all patients mounted an immune response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine immune response longevity in this group may be limited, vaccine booster dose should be considered.

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

Factors Affecting Initial Humoral Immune Response to SARS-Cov-2 Vaccines among Patients with Inflammatory Bowel Diseases

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michael D. Kappelman ◽  
Kimberly N. Weaver ◽  
Xian Zhang ◽  
Xiangfeng Dai ◽  
Runa Watkins ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Inflammatory Bowel Diseases ◽  
Factors Affecting ◽  
Humoral Immune ◽  
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.

Probiotics and bowel inflammation

2006 ◽  
Vol 247 ◽  
pp. 1-4
Keyword(s):  
Ulcerative Colitis ◽  
Immune Response ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Safety Issues ◽  
Bowel Diseases ◽  
Inflammatory Bowel

In a nutshellInflammatory bowel diseases can involve problems in the development of the gut's immune response. A healthy bowel flora plays an important role in this development, for example through effects on cytokines.Clinical trials of probiotics for IBD have been predominantly positive for ulcerative colitis and pouchitis, less so for Crohn's disease. So far probiotics appear to be a notably safe therapy, although some theoretical safety issues need to be borne in mind.

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
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