BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD...BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD)is a major differential diagnosis of CEAS,because these diseases share some clinical features.Therefore,there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM)can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1.We measured the concentration of PGEMUM in spot urine by radioimmunoassay,and the concentration was compared between the two groups of patients.We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC)curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9μg/g×Cre,P<0.0001).One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS[95%confidence interval(CI)3.2-16.7].A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6,95%CI 4.7-185.7).ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9μg/g×Cre with 95.0%sensitivity and 79.6%specificity.CONCLUSION PGE-MUM measurement is a convenient,non-invasive and useful test for the distinction of CEAS from CD.展开更多
Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
基金Supported by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development(AMED),No.15ek0109053h0002 to Matsumoto Tby grants from the Japan Society for the Promotion of Science(JSPS)KAKENHI,No.25460953,to Umeno J,Esaki M,and Matsumoto T
文摘BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS).Crohn's disease(CD)is a major differential diagnosis of CEAS,because these diseases share some clinical features.Therefore,there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM)can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1.We measured the concentration of PGEMUM in spot urine by radioimmunoassay,and the concentration was compared between the two groups of patients.We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC)curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9μg/g×Cre,P<0.0001).One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS[95%confidence interval(CI)3.2-16.7].A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6,95%CI 4.7-185.7).ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9μg/g×Cre with 95.0%sensitivity and 79.6%specificity.CONCLUSION PGE-MUM measurement is a convenient,non-invasive and useful test for the distinction of CEAS from CD.
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
