Biomarkers for Optimization and Personalization of Anti-TNFs in Pediatric Inflammatory Bowel Disease.
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ABSTRACT:
SUBMITTER: Salvador-Martin S
PROVIDER: S-EPMC8617733 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Inflammatory bowel disease (IBD) is a chronic disease mostly involved with intestine with unknown etiology. Diagnosis, evaluation of severity, and prognosis are still present as challenges for physicians. An ideal biomarker with the characters such as simple, easy to perform, noninvasive or microinvasive, cheap, rapid, and reproducible is helpful for patients and clinicians. Currently biomarkers applied in clinic include CRP, ESR, pANCA, ASCA, and fecal calprotectin. However, they are far from ideal. Lots of studies are focused on seeking for ideal biomarker for IBD. Herein, the paper reviewed recent researches on biomarkers of IBD to get advances of biomarkers in inflammatory bowel disease.
| S-EPMC4055235 | biostudies-literature
Project description:UnlabelledIn adult inflammatory bowel disease (IBD) patients, there is a strong discrepancy between symptoms and biomarkers of inflammation. Data on pediatric IBD patients are conflicting. Therefore, we aimed to investigate the relationship between clinical symptoms and biomarkers of inflammation in pediatric IBD. Patients aged <18 years with previously diagnosed Crohn's disease (CD) or ulcerative colitis (UC) were included. Clinical disease activity was determined using the abbreviated Pediatric CD Activity Index (aPCDAI) or Pediatric UC Activity Index (PUCAI). Biochemical disease activity was assessed using fecal calprotectin (FC) and C-reactive protein (CRP). In total, 127 patients (62 male; median age 14.9 years) were included (82 CD, 45 UC). FC correlated weakly with total aPCDAI score (r s = 0.32; 95 % CI 0.12-0.51; p = 0.003) and total PUCAI score (r s = 0.36; 95 % CI 0.07-0.62; p = 0.015). Only aPCDAI components abdominal examination and perirectal disease and PUCAI component activity level had a significant correlation with levels of FC. CRP correlated weakly with total aPCDAI score (r s = 0.28; 95 % CI 0.05-0.46; p = 0.012) and aPCDAI components abdominal examination and activity level. No significant correlation was observed between CRP and total PUCAI score (r s = 0.01; 95 % CI -0.34-0.29; p = 0.961) or individual PUCAI components.ConclusionThere is a strong discrepancy between clinical symptoms and biomarkers of inflammation in children with IBD.What is known• A substantial proportion of asymptomatic pediatric inflammatory bowel disease (IBD) patients have elevated biomarkers of inflammation. • There is a strong discrepancy between symptoms and biomarkers of inflammation in adults with IBD. What is New: • Clinical symptoms are only weakly associated with levels of fecal calprotectin and serum C-reactive protein in children and adolescents with previously diagnosed IBD. • Similarly to adult IBD patients, there is a strong discrepancy between clinical symptoms and biomarkers of inflammation in children with IBD.
| S-EPMC5031739 | biostudies-literature
Project description:Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids.Aims: To review the available data on serological biomarkers for IBD.Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD.Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management.Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
| S-EPMC7188783 | biostudies-literature
Project description:Background: In pediatric inflammatory bowel disease (IBD) up to 30% of patients do not respond to anti-TNF therapy. The aim was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: The study population included 29 responders and 9 non-responders to anti-TNF therapy patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Whole gene expression profiles from total RNA isolated from whole-blood samples of 6 responders and 6 non-responders taken before biologic administration and after 2 weeks were analyzed by RNA next-generation sequencing. The expression of 6 selected genes was measured for validation in all of 38 patients recruited using qPCR; Results: Differentially expressed genes in non-responders versus responders to anti-TNF treatment were identified, 32 prior treatment initiation and 44 after 2 weeks (Log2FC (Fold change)>0.6 o <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B and GBP1 were overexpressed in non-responders after 2 weeks of anti-TNF treatment (Log2FC 1.05, 1.21 and 1.08, respectively, p value <0.05,); Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
2021-01-14 | GSE159034 | GEO
Project description:BackgroundUp to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD.MethodsAn observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR.ResultsGenes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05).ConclusionExpression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
| S-EPMC7830359 | biostudies-literature
Project description:Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2-??Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.
| S-EPMC7247673 | biostudies-literature
Project description:Interindividual variation in response to anti-TNFalpha therapy may be explained by genetic variability in disease pathogenesis or mechanism of action. Recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) have increased our understanding of the genetic susceptibility to IBD. The aim was to test associations of known IBD susceptibility loci and novel "pharmacogenetic" GWAS identified loci with primary nonresponse to anti-TNFalpha in pediatric IBD patients and develop a predictive model of primary nonresponse.Primary nonresponse was defined using the Harvey Bradshaw Index (HBI) for Crohn's disease (CD) and partial Mayo score for ulcerative colitis (UC). Genotyping was performed using the Illumina Infinium platform. Chi-square analysis tested associations of phenotype and genotype with primary nonresponse. Genetic associations were identified by testing known IBD susceptibility loci and by performing a GWAS for primary nonresponse. Stepwise multiple logistic regression was performed to build predictive models.Nonresponse occurred in 22 of 94 subjects. Six known susceptibility loci were associated with primary nonresponse (P < 0.05). Only the 21q22.2/BRWDI loci remained significant in the predictive model. The most predictive model included 3 novel "pharmacogenetic" GWAS loci, the previously identified BRWD1, pANCA, and a UC diagnosis (R(2) = 0.82 and area under the curve [AUC] = 0.98%). The relative risk of nonresponse increased 15-fold when number of risk factors increased from 0-2 to > or =3.The combination of phenotype and genotype is most predictive of primary nonresponse to anti-TNFalpha in pediatric IBD. Defining predictors of response to anti-TNFalpha may allow the identification of patients who will not benefit from this class of therapy.
| S-EPMC2889173 | biostudies-literature
Project description:In inflammatory bowel disease (IBD), tumor necrosis factor plays an important role in mediating inflammation, but several other pathways are also involved in eliciting an inflammatory response. One such pathway is the invasion of the intestinal mucosa by leukocytes. Leukocytes within the systemic circulation move to sites of inflammation, and blocking this pathway could be an important treatment strategy for IBD. Anti-integrin therapy blocks the action of integrin on the surface of circulating immune cells and endothelial cell adhesion molecules, thereby inhibiting the interactions between leukocytes and intestinal blood vessels. Natalizumab, which acts on α4-integrin, was the first such drug to be approved for Crohn's disease, but its use is limited due to the risk of progressive multifocal leukoencephalopathy. Vedolizumab produces few systemic adverse effects because it acts on gut-trophic α4β7 integrin, and has been approved and is being used to treat IBD. Currently, several anti-integrin drugs, including etrolizumab, which acts on β7-integrin, and PF-00547569, which targets mucosal addressin cell adhesion molecule-1, are undergoing clinical trials and the results are being closely watched.
| S-EPMC5937204 | biostudies-literature
Project description:Although the impact of pediatric inflammatory bowel disease (IBD) extends beyond the patient to their parents and families, the focus of previous literature has largely been on investigating the patient's medical and psychosocial functioning, with less consideration of the family system. Having a comprehensive understanding of parent and family functioning within the context of pediatric IBD is important given the role parents and family members have in the successful management of the disease and caring of the child. The current review paper aggregates the empirical research regarding parent and family functioning, including comparisons to normative samples, other illness groups, and how functioning relates to child psychosocial and health outcomes. Extant literature on parents and families in pediatric IBD has largely focused on the variables of parenting stress, parent psychosocial functioning, parent quality of life, and family functioning. Summary findings elucidate the complex relationships between parents, families, and children affected by IBD and highlight the importance of assessing parent and family functioning within pediatric IBD. The current review also offers implications for clinical practice, notes the limitations of the present literature, and provides recommendations for future research.
| S-EPMC7603067 | biostudies-literature
Project description:The risk of venous thromboembolism (VTE) is significantly increased in patients with inflammatory bowel disease (IBD). For the adult population, prophylaxis guidelines exist to help guide physicians in their management of high-risk IBD patients. Although it is known that children with IBD also experience increased rates of VTE, there is no clear consensus on how best to prevent these unwanted complications. We sought to better understand practicing pediatric gastroenterologists' awareness of this issue and practices surrounding prevention of VTE in their pediatric patients. We found that pediatric gastroenterologists are well aware of the increased risk for VTE in children with IBD, that anticoagulant prophylaxis is infrequently used for pediatric patients, and that the most commonly cited reason for not providing prophylaxis is the lack of available guidelines in the literature.
| S-EPMC6612280 | biostudies-literature