Project description:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pre-transplant genetic susceptibility is evident in adult TA-TMA patients at the level of TMA-associated variants and further investigated the association of genetic variants with clinical outcomes. We studied 30 patients with TA-TMA at a median of 73 (9-540) post-transplant days, donors of 18/30 patients and 30 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pre-transplant peripheral blood was analyzed by targeted next generation sequencing for complement regulatory genes and ADAMTS13. Donors presented significantly lower frequency of rare variants (p=0.049) and variants in exonic/splicing/UTR regions (p=0.025), compared to TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13 (p=0.001), CD46 (p=0.002), CFH (p=0.010) and CFI (p=0.031). Pathogenic variants were found in ADAMTS13, CFH, CFI and CFB, while homozygous pathogenic variants in ADAMTS13 and CFB were evident in only 4 TA-TMA patients (p=0.038). Patients refractory to conventional treatment (70%) were significantly (p=0.045) enriched for variants in exonic/splicing/UTR regions compared to responders. Nineteen of 30 patients (63%) succumbed to transplant-related mortality, which was also associated with significantly (p=0.012) increased frequency of variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pre-transplant genomic screening may be useful to intensify monitoring and early intervention in high-risk patients.

2019-04-18 | E-MTAB-7848 | biostudies-arrayexpress

NGS in hematopoietic cell transplant recipients

Project description:NGS in hematopoietic cell transplant recipients

| PRJEB32082 | ENA

Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

Project description:The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

| 2262897 | ecrin-mdr-crc

Gut microbiota associated with organ transplant outcome

Project description:Gut microbiota associated with organ transplant outcome Targeted loci environmental

| PRJNA480643 | ENA

STAMPEED: Family Heart Study SCAN - Genome Association Scan for Atherosclerosis Pathway Genes (Caucasians)

Project description:STAMPEED: Family Heart Study SCAN - Genome Association Scan for Atherosclerosis Pathway Genes (Caucasians)

| PRJNA75565 | ENA

DNA Methylation Dynamics in Blood after Hematopoietic Cell Transplant

Project description:Classically, epigenetic deregulation is considered a common hallmark of cancer. Nevertheless, recent publications have demonstrated its association with a large array of human diseases such as autoimmune disorders and environmental factors such as diet. Despite the increasing relevance of DNA methylation for the study of critical biological processes and for the development of novel biomarkers, DNA methylation analysis applied to the study of hematopoietic cell transplantation (HCT) has not yet been explored. Here, we analyzed global DNA methylation in blood samples by using a pyrosequencing based methylation assay of repetitive DNA elements (LINE1 and NBL2) in a cohort of 47 patients with allogenic HCT up to 12 months post-HCT. We observed that the recipients stably maintained the donor’s global methylation levels after transplant. Nonetheless, NBL2 methylation is affected by physiopathological events such as development of mixed chimerism. Microarray-based DNA methylation analysis of promoters revealed that methylation in more than 200 genes is altered 1 month post-HCT when compared with non-pathological methylation levels in the donor’s blood. Interestingly, this number dramatically decreased by 6 months post-HCT. Finally, based in the microarray data, we analyzed by pyrosequencing DNA methylation in IFN-γ, FASL, and IL-10 and found a statistically significant association between methylation in these immune genes and the severity of the acute graft-versus-host disease. In conclusion, our results provide strong evidence that DNA methylation changes in blood are linked to underlying physiological events and demonstrate that DNA methylation analysis is a viable strategy for the study of hematopoietic cell transplantation and for development of biomarkers. Bisulphite converted DNA from 6 blood samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

2013-02-27 | E-GEOD-36832 | biostudies-arrayexpress