Plasma biomarkers of lower gastrointestinal and liver acute GVHD.
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ABSTRACT:
SUBMITTER: Harris AC
PROVIDER: S-EPMC3327467 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intestinal graft-versus-host disease (GVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation. The intestinal mucosa comprises the inner lining of the intestinal tract and maintains close proximity with commensal microbes that reside within the intestinal lumen. Recent advances have significantly improved our understanding of the interactions between the intestinal mucosa and the enteric microbiota. Changes in host mucosal tissue and commensals posttransplant have been actively investigated, and provocative insights into mucosal immunity and the enteric microbiota are now being translated into clinical trials of novel approaches for preventing and treating acute GVHD. In this review, we summarize recent findings related to aspects of the intestinal mucosa during acute GVHD.
| S-EPMC5575743 | biostudies-literature
Project description:Intestinal graft-versus-host disease (GVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation. The intestinal mucosa comprises the inner lining of the intestinal tract and maintains close proximity with commensal microbes that reside within the intestinal lumen. Recent advances have significantly improved our understanding of the interactions between the intestinal mucosa and the enteric microbiota. Changes in host mucosal tissue and commensals posttransplant have been actively investigated, and provocative insights into mucosal immunity and the enteric microbiota are now being translated into clinical trials of novel approaches for preventing and treating acute GVHD. In this review, we summarize recent findings related to aspects of the intestinal mucosa during acute GVHD.
| S-EPMC5114486 | biostudies-literature
Project description:Lower gastrointestinal (GI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic stem cell transplantation. Recent data indicate that lower GI tract GVHD is a complicated process mediated by donor/host antigenic disparities. This process is exacerbated by significant changes to the microbiome, and innate and adaptive immune responses that are critical to the induction of disease, persistence of inflammation, and a lack of response to therapy. Here, we discuss new insights into the biology of lower GI tract GVHD and focus on intrinsic pathways and regulatory mechanisms crucial to normal intestinal function. We then describe multiple instances in which these homeostatic mechanisms are altered by donor T cells or conditioning therapy, resulting in exacerbation of GVHD. We also discuss data suggesting that some of these mechanisms produce biomarkers that could be informative as to the severity of GVHD and its response to therapy. Finally, novel therapies that might restore homeostasis in the GI tract during GVHD are highlighted.
| S-EPMC5490758 | biostudies-literature
Project description:Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-host-disease
| PRJEB39834 | ENA
Project description:Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n = 236) and 2 validation cohorts separated in time (n = 142 and n = 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3?) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P = .004) and for Minnesota risk (0.72, P = .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies.
| S-EPMC6014357 | biostudies-literature
Project description:BackgroundTreatment of IBS and functional lower gastrointestinal disorders is still based predominantly on symptoms; biomarkers that reflect the mechanism or pathophysiology have been identified. Given the diverse mechanisms that result in the same clinical phenotype of IBS, it is hypothesised that identification of biomarkers may lead to individualisation of medical therapy.AimTo review the biomarkers that have been appraised in IBS.MethodsA single author reviewed the published literature on biomarkers appraised in IBS.ResultsThe current literature suggests that these biomarkers are insufficiently sensitive or specific to differentiate IBS from health or from other diseases causing similar symptoms, such as coeliac disease or inflammatory bowel disease. Most of the proposed biomarkers are not actionable, that is, they do not lead to an efficacious therapy based on the biological inference of the biomarker itself. However, among proposed biomarkers in IBS, some are actionable, as they specifically reflect a quantitative difference in a mediator of dysfunction or result in a quantifiable disturbance of function that can be specifically treated. Such biomarkers may potentially identify relevant subgroups that respond to specific therapy. The most promising actionable biomarkers are measurement of colonic transit (leading to treatments that reverse the abnormal transit) and measurements of bile acid diarrhoea to identify responders to bile acid sequestrants.ConclusionsTherefore, although biomarkers are not ready for prime time as diagnostic tests in IBS, some biomarkers could identify subgroups of patients with IBS for inclusion in clinical trials that target specific dysfunctions. Such an approach may enhance treatment efficacy, and may ultimately help reduce costs in drug development and in the management of patients in clinical practice.
| S-EPMC4558225 | biostudies-literature
Project description:BACKGROUND:There are very few studies investigating metabolic biomarkers to predict acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Metabolic models can provide a framework for analyzing the information-rich omics data sets in this setting. METHODS:Four hundred and fifty-six samples from one hundred and fourteen consecutive patients who underwent HSCT from January 2012 to May 2014 were collected for this study. The changes in serum metabolite levels were investigated using a gas chromatography-mass spectrometry-based metabolomics approach and underwent statistical analysis. RESULTS:Significant metabolic changes were observed on day 7. The stearic acid/palmitic acid (SA/PA) ratio was effective in the diagnosis of grade II-IV aGVHD. Multivariate analysis showed that patients with high SA/PA ratios on day 7 after HSCT were less likely to develop II-IV aGVHD than patients with low SA/PA ratios (odds ratio [OR] = 0.06, 95% CI 0.02-0.18, P < 0.001). After the adjustment for clinical characteristics, the SA/PA ratio had no significant effect on overall survival (hazard ratio [HR] = 1.95, 95% CI 0.92-4.14, P = 0.08), and patients in the high SA/PA ratio group were significantly more likely to relapse than those in the low ratio group (HR = 2.26, 95% CI 1.04-4.91, P = 0.04). CONCLUSION:Our findings suggest that the SA/PA ratio on day 7 after HSCT is an excellent biomarker to predict both aGVHD and relapse. The serum SA/PA ratio measured on day 7 after transplantation may improve risk stratification for aGVHD and relapse after allogeneic stem cell transplantation. FUNDING:National Natural Science Foundation of China (81470346, 81773361), Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Natural Science Foundation (BK20161204), Innovation Capability Development Project of Jiangsu Province (BM2015004), Jiangsu Medical Junior Talent Person award (QNRC2016707), and NIH (AI129582 and NS106170).
| S-EPMC6012513 | biostudies-literature
Project description:The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR-/- T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4+ T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pTreg) cells in the colon of recipients transplanted with AhR-/- T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible Treg (iTreg) cells from naïve CD4+ human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.
| S-EPMC5520467 | biostudies-literature
Project description:Lower gastrointestinal (GI) bleeding is a well-known symptom of colorectal cancer (CRC). Whether incident GI bleeding is also a marker of other GI cancers remains unclear.This nationwide cohort study examined the risk of various GI cancer types in patients with lower GI bleeding. We used Danish medical registries to identify all patients with a first-time hospital diagnosis of lower GI bleeding during 1995-2011 and followed them for 10 years to identify subsequent GI cancer diagnoses. We computed absolute risks of cancer, treating death as a competing risk, and calculated standardized incidence ratios (SIRs) by comparing observed cancer cases with expected cancer incidence rates in the general population.Among 58,593 patients with lower GI bleeding, we observed 2,806 GI cancers during complete 10-year follow-up. During the first year of follow-up, the absolute GI cancer risk was 3.6%, and the SIR of any GI cancer was 16.3 (95% confidence interval (CI): 15.6-17.0). Colorectal cancers accounted for the majority of diagnoses, but risks of all GI cancers were increased. During 1-5 years of follow-up, the SIR of any GI cancer declined to 1.36 (95% CI: 1.25-1.49), but risks remained increased for several GI cancers. Beyond 5 years of follow-up, the overall GI cancer risk was close to unity, with reduced risk of rectal cancer and increased risk of liver and pancreatic cancers.A hospital-based diagnosis of lower GI bleeding is a strong clinical marker of prevalent GI cancer, particularly CRC. It also predicts an increased risk of any GI cancer beyond 1 year of follow-up.
| S-EPMC4855159 | biostudies-other
Project description:BACKGROUND AND STUDY AIMS:?Investigations for lower gastrointestinal bleeding (LGIB) include flexible sigmoidoscopy, colonoscopy, computed tomographic angiography (CTA), and angiography. All may be used to direct endoscopic, radiological or surgical treatment, although their optimal use is unknown. The aims of this study were to determine the diagnostic and therapeutic yields of endoscopy, CTA, and angiography for managing LGIB, and their influence on rebleeding, transfusion, and hospital stay. PATIENTS AND METHODS:?A systematic search of MEDLINE, PubMed, EMBASE, and CENTRAL was undertaken to identify randomized controlled trials (RCTs) and nonrandomized studies of intervention (NRSIs) published between 2000 and 12 November 2015 in patients hospitalized with LGIB. Separate meta-analyses were conducted, presented as pooled odds (ORs) or risk ratios (RR) with 95?% confidence intervals (CIs). RESULTS:?Two RCTs and 13 NRSIs were included, none of which examined flexible sigmoidoscopy, or compared endotherapy with embolization, or investigated the timing of CTA or angiography. Two NRSIs (57?-?223 participants) comparing colonoscopy and CTA were of insufficient quality for synthesis but showed no difference in diagnostic yields between the two interventions. One RCT and 4 NRSIs (779 participants) compared early colonoscopy (<?24 hours) with colonoscopy performed later; meta-analysis of the NRSIs demonstrated higher diagnostic and therapeutic yields with early colonoscopy (OR 1.86, 95?%CI 1.12 to 2.86, P ?=?0.004 and OR 3.08, 95?%CI 1.93 to 4.90, P ?<?0.001, respectively) and reduced length of stay (mean difference 2.64 days, 95?%CI 1.54 to 3.73), but no difference in transfusion or rebleeding. CONCLUSIONS:?In LGIB there is a paucity of high-quality evidence, although the limited studies on the timing of colonoscopy suggest increased rates of diagnosis and therapy with early colonoscopy.
| S-EPMC5624283 | biostudies-literature