DNA Methylation of Colon Mucosa in Ulcerative Colitis Patients: Correlation with Inflammatory Status

Background: Although DNA methylation of colonic mucosa in ulcerative colitis (UC) has been suggested, the majority of published reports indicate the correlation between methylation of colon mucosa and occurrence of UC-related dysplasia or cancer without considering the mucosal inflammatory status. The aim of this study was to verify whether mucosal inflammation-specific DNA methylation occurs in the colon of UC. Methods: Of 15 gene loci initially screened, six loci (ABCB1, CDH1. ESR1, GDNF, HPP1, and MYOD1) methylated in colon mucosa of UC were analyzed according to inflammatory status using samples from 28 surgically resected UC patients. Results: Four of six regions (CDH1, GDNF, HPP1, and MYOD1) were more highly methylated in the active inflamed mucosa than in the quiescent mucosa in each UC patient (P = 0.003, 0.0002, 0.02, and 0.048, respectively). In addition, when the methylation status of all samples taken from examined patients was stratified according to inflammatory status, methylation of CDHI and GDNF loci was significantly higher in active inflamed mucosa than in quiescent mucosa (P = 0.045 and 0.002, respectively). Multiple linear regression analysis revealed that active inflammation was an independent factor of methylation for CDHI and GDNF. DNA methyltransferase 1 and 3b were highly expressed in colon epithelial cells with active mucosa] inflammation, suggesting their involvement in inflammation-dependent methylation. Conclusions: Methylation in colonic mucosa of UC was correlated with mucosal inflammatory status, suggesting the involvement of methylation due to chronic active inflammation in UC carcinogenesis

A case of progressive multifocal leukoencephalopathy in a post-kidney transplant patient with improvement after discontinuation of immunosuppressive drugs and combination therapy with mefloquine and mirtazapine

Abstract Background Progressive multifocal leukoencephalopathy is a rare disease, but the prognosis is very poor, especially in the immunosuppressed state with a non-HIV background, and there is no established treatment. Case presentations A 49-year-old patient who had undergone a renal transplant and was receiving prednisolone and mycophenolate mofetil treatment was admitted for peritoneal dialysis initiation. While hospitalized, he experienced aphasia and other percutaneous symptoms. Magnetic resonance imaging of the brain revealed a subcortical demyelinating lesion. JC virus DNA was identified in cerebrospinal fluid, and he was diagnosed with progressive multifocal leukoencephalopathy. Immunosuppressant was ceased, and he was treated with mefloquine and mirtazapine. The patient subsequently underwent a head MRI scan, confirming lesion reduction, improved activities of daily life, and survival. Conclusions Progressive multifocal leukoencephalopathy is commonly observed in patients with compromised immune systems, which was the case for this patient due to long-standing immunosuppressive medication usage and end-stage renal failure necessitating dialysis