BACKGROUND: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
- MeSH
- adaptivní imunita MeSH
- imunitní systém * embryologie růst a vývoj MeSH
- imunomodulace MeSH
- lidé MeSH
- lymfocyty MeSH
- mateřské mléko imunologie MeSH
- mikrobiota MeSH
- novorozenec imunologie MeSH
- přirozená imunita MeSH
- Check Tag
- lidé MeSH
- novorozenec imunologie MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting mainly preterm newborns. It is characterized by unexpected onset and rapid progression with specific diagnostic signs as pneumatosis intestinalis or gas in the portal vein appearing later in the course of the disease. Therefore, we analyzed diagnostic and prognostic potential of the markers of early NEC pathogenesis, such as excessive inflammatory response (serum amyloid A (SAA)) and gut epithelium damage (intestinal and liver fatty acid-binding protein (I-FABP and L-FABP, respectively) and trefoil factor-3 (TFF-3)). We used ELISA to analyze these biomarkers in the urine of patients with suspected NEC, either spontaneous or surgery-related, or in infants without gut surgery (controls). Next, we compared their levels with the type of the disease (NEC or sepsis) and its severity. Already at the time of NEC suspicion, infants who developed NEC had significantly higher levels of all tested biomarkers than controls and higher levels of I-FABP and L-FABP than those who will later develop sepsis. Infants who will develop surgery-related NEC had higher levels of I-FABP and L-FABP than those who will develop sepsis already during the first 6 hours after the abdominal surgery. I-FABP was able to discriminate between infants who will develop NEC or sepsis and the SAA was able to discriminate between medical and surgical NEC. Moreover, the combination of TFF-3 with I-FABP and SAA could predict pneumatosis intestinalis, and the combination of I-FABP, L-FABP, and SAA could predict gas in the portal vein or long-term hospitalization and low SAA predicts early full enteral feeding. Thus, these biomarkers may be useful not only in the early, noninvasive diagnostics but also in the subsequent NEC management.
- MeSH
- biologické markery moč MeSH
- časná diagnóza MeSH
- diferenciální diagnóza MeSH
- faktor TFF3 moč MeSH
- lidé MeSH
- nekrotizující enterokolitida diagnóza MeSH
- novorozenec MeSH
- prognóza MeSH
- progrese nemoci MeSH
- proteiny vázající mastné kyseliny moč MeSH
- sepse diagnóza MeSH
- sérový amyloid A moč MeSH
- střevní sliznice patologie MeSH
- vény fyziologie MeSH
- zánět diagnóza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.
- MeSH
- biologické markery krev MeSH
- Crohnova nemoc komplikace diagnóza metabolismus MeSH
- dospělí MeSH
- dysbióza komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- sklerozující cholangitida komplikace MeSH
- ulcerózní kolitida komplikace diagnóza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- střevní bariéra,
- MeSH
- akutní nemoc MeSH
- dysbióza MeSH
- enterální výživa škodlivé účinky MeSH
- imunitní systém imunologie MeSH
- kathelicidiny fyziologie imunologie MeSH
- lidé MeSH
- nekrotizující enterokolitida * etiologie imunologie patofyziologie MeSH
- novorozenec nedonošený MeSH
- novorozenec s nízkou porodní hmotností MeSH
- novorozenec MeSH
- Panethovy buňky fyziologie imunologie MeSH
- rizikové faktory MeSH
- střevní mikroflóra * imunologie MeSH
- střevní sliznice * fyziologie imunologie růst a vývoj MeSH
- trávicí systém - fyziologické jevy imunologie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Necrotizing enterocolitis (NEC) is severe disease of gastrointestinal tract, yet its early symptoms are nonspecific, easily interchangeable with sepsis. Therefore, reliable biomarkers for early diagnostics are needed in clinical practice. Here, we analyzed if markers of gut mucosa damage, caspase cleaved cytokeratin 18 (ccCK18) and intestinal fatty acid-binding protein (I-FABP), could be used for differential diagnostics of NEC at early stage of disease. We collected paired serum (at enrollment and week later) and urine (collected for two days in 6 h intervals) samples from 42 patients with suspected NEC. These patients were later divided into NEC (n = 24), including 13 after gastrointestinal surgery, and sepsis (n = 18) groups using standard criteria. Healthy infants (n = 12), without any previous gut surgery, served as controls. Both biomarkers were measured by a commercial ELISA assay. There were no statistically significant differences in serum ccCK18 between NEC and sepsis but NEC patients had significantly higher levels of serum and urinary I-FABP than either sepsis patients or healthy infants. Urinary I-FABP has high sensitivity (81%) and specificity (100%) and can even distinguish NEC from sepsis in patients after surgery. Urinary I-FABP can be used to distinguish NEC from neonatal sepsis, including postoperative one, better than abdominal X-ray.
- MeSH
- biologické markery moč MeSH
- časná diagnóza MeSH
- diferenciální diagnóza MeSH
- keratin-18 moč MeSH
- kojenec MeSH
- lidé MeSH
- nekrotizující enterokolitida diagnóza patologie moč MeSH
- proteiny vázající mastné kyseliny moč MeSH
- sepse diagnóza patologie moč MeSH
- studie případů a kontrol MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
