Cross-organ hierarchy of HLA molecular mismatches in donor-specific antibody development in solid organ transplantations.

Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) play a crucial role in antibody-mediated rejection, a major barrier to successful organ transplantation. Donor-recipient HLA molecular incompatibility critically influences DSA susceptibility, commonly assessed by analyzing mismatches in the HLA eplet repertoire. This study, including six distinct liver, lung, and kidney transplant cohorts from two centers (978 donor-recipient pairs), explores associations between individual eplet mismatches and DSA development.

Effect of HLA Genotype on Anti-PD-1 Antibody Treatment for Advanced Renal Cell Carcinoma in the SNiP-RCC Study.

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021.

Development and nationwide validation of kidney graft injury markers using urinary exosomes and microvesicles (complete English translation of the Japanese version).

Background: Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients.

Methods: One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies.

Impact of germline HLA genotypes on clinical outcomes in patients with urothelial cancer treated with pembrolizumab.

Human leukocyte antigen class I (HLA-I) genotypes are suggested to influence the cancer response to checkpoint blockade immunotherapy. This study assessed the impact of germline HLA genotypes on clinical outcomes in patients with chemoresistant advanced urothelial cancer (UC) treated with pembrolizumab. Zygosity, supertypes, evolutionary divergency, and specific alleles of germline HLA-I and -II were evaluated using the Luminex technique in 108 patients with chemoresistant metastatic or locally advanced UC treated with pembrolizumab.

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients.

Background: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the effects of TLTs on future graft function using our histologic TLT maturity stages and the association between TLTs and Banff pathologic scores.

Effect of HLA genotype on intravesical recurrence after bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer.

The intravesical administration of bacillus Calmette-Guérin (BCG) is widely used to control the intravesical recurrence of non-muscle-invasive bladder cancer (NMIBC). This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for NMIBC. This study included Japanese patients who had received intravesical BCG for NMIBC.

Tacrolimus concentrations after renal transplantation in a mother-neonate dyad: Maternal, neonatal and breast milk measurements.

What Is Known And Objective: We aim to add to the few reports on tacrolimus concentrations in breast milk and in maternal, umbilical vein and neonatal blood after maternal renal transplantation.

Case Summary: In a 30-year-old pregnant woman, the tacrolimus concentration at delivery was the same in maternal, umbilical vein and neonatal blood. The breast milk/maternal blood tacrolimus ratio ranged from 0.

Loss of antibodies to hepatitis E virus in organ transplant patients with hepatitis E.

Aim: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey.

Methods: This study was undertaken from 2012 to 2019.

Association of immunosuppressive agents and cytomegalovirus infection with de novo donor-specific antibody development within 1 year after renal transplantation.

The association between immunosuppressive therapy or cytomegalovirus (CMV) infection and detection of de novo donor-specific antibody (dnDSA) at 1 year after transplantation was evaluated. The impact of dnDSA positivity at 1 year after transplantation on long-term death-censored renal graft survival was also evaluated. One hundred and sixty adults receiving living renal allografts were studied.

Impact of persistent preformed and de novo donor-specific antibodies detected at 1 year after kidney transplantation on long-term graft survival in Japan: a retrospective study.

Background: We evaluated the impact of persistent preformed donor-specific antibody (DSA) and de novo DSA (dnDSA) detected at 1 year posttransplantation on long-term death-censored graft survival.

Methods: One hundred and sixty adult patients who received living kidney allograft with pretransplant-negative T-cell complement-dependent cytotoxicity crossmatch (CDCXM), and without periodic screening for DSA, were eligible for this study. All enrolled patients were retrospectively tested for DSA using the Luminex assay.

A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis in Heart and Kidney Transplant Recipients in Japan.

Background: Recently, chronic hepatitis E has been reported in solid organ transplant (SOT) recipients in European countries. Previously, we clarified the prevalence of hepatitis E virus (HEV) infection in Japanese liver transplant recipients and identified 2 chronic hepatitis E patients infected by blood transfusion. However, the rate of HEV infection in recipients of SOTs other than liver in Japan remains unclear, so we conducted a nationwide survey to clarify the prevalence of chronic HEV infection in Japanese heart and kidney transplant recipients.

Contribution of UGT1A1 genetic polymorphisms related to axitinib pharmacokinetics to safety and efficacy in patients with renal cell carcinoma.

Axitinib is a potent second-line molecular-targeted agent for metastatic renal cell carcinoma (mRCC). Axitinib pharmacokinetics and its relation with genetic polymorphisms were evaluated to predict the adverse events (AEs) and efficacy of axitinib. We analyzed 46 patients with mRCC who were treated with axitinib.

The mechanism of the down-regulation of hepatic transporters in rats with indomethacin-induced intestinal injury.

Background: Previously, we reported that hepatic transporters were down-regulated consistent with intestinal injury in indomethacin (IDM)-treated rats.

Aim: The purpose of this study was to characterize this mechanism of the down-regulation of hepatic transporters in IDM-treated rats.

Methods: Hepatic nuclear receptor expressions, oxidative stress condition and the expression of hepatic transporters were evaluated in rats with IDM-induced intestinal injury with or without the administration of mucosal protectant ornoprostil, a prostaglandin E1 analogue, or aminoguanidine (AG), an iNOS inhibitor.

Involvement of carboxylesterase 1 and 2 in the hydrolysis of mycophenolate mofetil.

Mycophenolate mofetil (MMF) is the ester prodrug of the immunosuppressant agent mycophenolic acid (MPA) and is rapidly activated by esterases after oral administration. However, the role of isoenzymes in MMF hydrolysis remains unclear. Although human plasma, erythrocytes, and whole blood contain MMF hydrolytic activities, the mean half-lives of MMF in vitro were 15.

Down-regulation of hepatic transporters for BSP in rats with indomethacin-induced intestinal injury.

Previous reports have demonstrated that an intestinal injury causes hypofunctions of the liver associated with down-regulations of cytochrome P450, but an influence on hepatic transporters remains unclear. Here, we tested hepatic transporter functions in a rat model of bowel injury using indomethacin (IDM). After administration of IDM (8.

Involvement of human blood arylesterases and liver microsomal carboxylesterases in nafamostat hydrolysis.

Metabolism of nafamostat, a clinically used serine protease inhibitor, was investigated with human blood and liver enzyme sources. All the enzyme sources examined (whole blood, erythrocytes, plasma and liver microsomes) showed nafamostat hydrolytic activity. V(max) and K(m) values for the nafamostat hydrolysis in erythrocytes were 278 nmol/min/mL blood fraction and 628 microM; those in plasma were 160 nmol/min/mL blood fraction and 8890 microM, respectively.