Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn’s disease patients

Łykowska‐Szuber, Liliana; Walczak, Mateusz; Dobrowolska, Agnieszka; Skrzypczak-Zielińska, Marzena

doi:10.1097/meg.0000000000002618

Cited by 3 publications

(2 citation statements)

References 75 publications

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“…Decreases in the levels of caspase and TNF-α, which are responsible for apoptosis, may play an effective role in the treatment mechanism of CD (Lykowska-Szuber et al 2023). In this study, similar to the findings of other studies, it was determined that caspase levels were lower in the groups receiving vitamin D and UD compared to the TNBS group.…”

Section: Discussionsupporting

confidence: 85%

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Effect of vitamin D<sub>3</sub> and a stinging nettle extract on the gastric tissue of rats administered with trinitrobenzene sulfonic acid

Gezer,

Yediel Aras,

Kilic Baygutalp

et al. 2024

Vet. Med. - Czech

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In this study, the effects of vitamin D 3 (Vit. D) and a stinging nettle [ Urtica dioica L. (UD)] extract were examined using histopathological and immunohistochemical methods in the stomach tissues of an experimentally created rat model of Crohn’s disease (CD). The CD model was created using trinitrobenzene sulfonic acid (TNBS). The animals in the study were divided into control, TNBS, TNBS+Vit. D, and TNBS+UD groups. At the end of the experiment, the animals were euthanised and their stomach tissues were evaluated for necrosis, degeneration, apoptosis, and inflammation. Additionally, an immunohistochemical method was applied to determine the somatostatin (SSTR), aquaporin-1 (AQP-1), caspase-3, and tumour necrosis factor-alpha (TNF-α) immunoreactivity in the gastric tissues. In the evaluations, degenerative and necrotic changes and mononuclear cell infiltration areas were observed in the TNBS group, but such changes could be improved with Vit. D and UD applications. The results suggest that the combination of the Vit. D and UD extract may have a protective and therapeutic role in mitigating TNBS-induced damage to the gastric tissues, potentially through the regulation of SSTR, AQP-1, caspase-3, and TNF-α expression. This indicates a promising avenue for further research and the exploration of these compounds in the context of gastrointestinal health.

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Section: Discussionsupporting

confidence: 85%

“…Decreases in the levels of caspase and TNF-α, which are responsible for apoptosis, may play an effective role in the treatment mechanism of CD ( Lykowska-Szuber et al. 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of vitamin D<sub>3</sub> and a stinging nettle extract on the gastric tissue of rats administered with trinitrobenzene sulfonic acid

Gezer,

Yediel Aras,

Kilic Baygutalp

et al. 2024

Vet. Med. - Czech

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Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn’s disease patients

Lykowska-Szuber,

Walczak,

Stawczyk-Eder

et al. 2023

J Appl Genetics

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Anti-tumor necrosis factor (TNF) therapy is used to induce and maintain remission in Crohn’s disease (CD) patients. However, primary non-responders to initial treatment constitute 20–40% of cases. The causes of this phenomenon are still unknown. We aim to investigate the impact of the caspase 9 (CASP9) gene variants on the variable reactions of CD patients to anti-TNF therapy. The study group included 196 diagnosed and clinically characterized CD Polish patients following anti-TNF therapy. The sequence of the CASP9 gene was analyzed using next-generation and Sanger sequencing and was analyzed with the response to biological treatment. Using the RT-qPCR analysis, we estimated the CASP9 gene mRNA level in colon biopsies material from inflamed and non-inflamed tissue (21 CD patients: 14 responders and seven non-responders to anti-TNF therapy and six controls), as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls. Our findings indicated association of variants rs1052571 and rs4645978 with response to anti-TNF monoclonal antibodies (mAbs). Moreover, we observed tendency for reduced expression after incubation with anti-TNF in the group of CD patients, in contrast to the control group. Our results suggest that response to anti-TNF therapy in CD patients may be an effect of variants of the CASP9 gene as a key effector of the internal pathway of apoptosis; however, further population and functional research are necessary.

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Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn's disease patients

Łykowska‐Szuber

Walczak²,

Stawczyk‐Eder

et al. 2023

Preprint

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Anti-tumor necrosis factor (TNF) therapy is used to induce and maintain remission in Crohn’s disease (CD) patients. However, primary non-responders to initial treatment constitute 20–40% of cases. The causes of this phenomenon are still unknown. We aim to investigate the impact of the caspase 9 (CASP9) gene variants on the variable reactions of CD patients to anti-TNF therapy. The study group included 196 diagnosed and clinically characterized CD Polish patients following anti-TNF therapy. The sequence of the CASP9 gene was analyzed using next-generation and Sanger sequencing and was analyzed with the response to biological treatment. Using the RT-qPCR analysis, we estimated the CASP9 gene mRNA level in colon biopsies material from inflamed and non-inflamed tissue (21 CD patients: 14 responders and seven non-responders to anti-TNF therapy and six controls), as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls. Our findings indicated association of variants rs1052571 and rs4645978 with response to anti-TNF monoclonal antibodies (mAbs). Moreover, we observed tendency for reduced expression after incubation with anti-TNF in the group of CD patients, in contrast to the control group. Our results suggest that response to anti-TNF therapy in CD patients may be an effect of variants of the CASP9 gene as a key effector of the internal pathway of apoptosis, however, further population and functional research are necessary.

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Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn’s disease patients

Cited by 3 publications

References 75 publications

Effect of vitamin D<sub>3</sub> and a stinging nettle extract on the gastric tissue of rats administered with trinitrobenzene sulfonic acid

Effect of vitamin D<sub>3</sub> and a stinging nettle extract on the gastric tissue of rats administered with trinitrobenzene sulfonic acid

Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn’s disease patients

Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn's disease patients

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