Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease
Abstract
:1. Introduction
2. Materials and Methods
3. Genetic Polymorphisms
- Human Leukocyte Antigens variants
- Other Polymorphisms
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- Polymorphisms of the TNFα gene (leading to increased cytokine secretion) and TNFα receptors genes (TNFR1/2, resulting in increased response after interaction with TNFα).
- -
- Polymorphisms of innate immunity-related genes (TLR4, CD14, IL-6, and IL-1β).
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- Polymorphisms of apoptosis- and autophagy-related genes (FASL, CASP9 and ATG16L1), probably through an inhibitory effect on the apoptosis of immune cells.
4. Transcriptional Profiles
5. Epigenetic Modifications
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- There were 26 associated with specific immune compartment cells (B cells, T cells, granulocytes, and monocytes).
- -
- A further 125 had been previously associated by epigenome-wide association studies (EWAS) with alcohol consumption, body mass index, smoking, C reactive protein, and IBD type [72].
6. Other Mechanisms
7. Conclusions, Limitations and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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SNPs | Molecule | Disease | Drug | Effect | References |
---|---|---|---|---|---|
rs2097432 | HLA-DQA1*05 | P-UC P-CD UC CD | IFX ADA | Decreased response | [10,14] |
rs2395185 | HLA-DRB9 | P-UC P-CD | IFX | Decreased response | [13,14] |
rs1052571 rs4645978 | CASP9 | CD | IFX ADA | Increased response | [19] |
rs7234029 | PTPN2 | CD | UST | Decreased response | [20] |
rs442905 | C1orf106 | CD | IFX | Decreased IFX levels | [27] |
rs7587051 | ATG16L1 | CD | IFX | Decreased IFX levels | [27] |
rs3213448 | IL1RN | CD | IFX | Increased IFX levels | [27] |
rs5030728 | TLR4 | P-UC P-CD | IFX | Decreased IFX levels | [28] |
rs11465996 | LY96 | P-UC P-CD | IFX | Decreased IFX levels | [28] |
rs1816702 | TLR2 | P-UC P-CD | ADA | Decreased ADA levels | [28] |
rs3397 | TNFRSF1B | P-UC P-CD | ADA | Decreased ADA levels | [28] |
rs3024505 | IL-10 | CD | IFX | Decreased IFX levels | [29] |
SNPs | Molecule | Disease | Drug | Effect | References |
---|---|---|---|---|---|
rs1004819 rs2201841 rs10889677 rs11209032 rs1495965 | IL-23R | UC | IFX | Increased response | [33] |
rs7517847 rs10489629 rs11465804 rs1343151 | IL-23R | UC | IFX | Decreased response | [33] |
rs10489629 | IL-23R | CD | IFX | Increased response | [34] |
rs10489628 rs10789229 rs1343151 | IL-23R | P-CD | IFX | Increased IFX-induced psoriasis rates | [35] |
rs1004819 rs10889677 | IL-23R | UC | IFX | Increased EIMs rates | [36] |
rs11209026 | IL-23R | UC, CD, Psoriasis | IFX, ADA | Increased Anti-TNF-induced psoriasiform skin lesion rates; Increased risk of CD-related surgery | [38,39,40] |
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Puca, P.; Capobianco, I.; Coppola, G.; Di Vincenzo, F.; Trapani, V.; Petito, V.; Laterza, L.; Pugliese, D.; Lopetuso, L.R.; Scaldaferri, F. Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease. Int. J. Mol. Sci. 2024, 25, 2789. https://doi.org/10.3390/ijms25052789
Puca P, Capobianco I, Coppola G, Di Vincenzo F, Trapani V, Petito V, Laterza L, Pugliese D, Lopetuso LR, Scaldaferri F. Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease. International Journal of Molecular Sciences. 2024; 25(5):2789. https://doi.org/10.3390/ijms25052789
Chicago/Turabian StylePuca, Pierluigi, Ivan Capobianco, Gaetano Coppola, Federica Di Vincenzo, Valentina Trapani, Valentina Petito, Lucrezia Laterza, Daniela Pugliese, Loris Riccardo Lopetuso, and Franco Scaldaferri. 2024. "Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease" International Journal of Molecular Sciences 25, no. 5: 2789. https://doi.org/10.3390/ijms25052789