Combined transcriptome and T cell receptor alpha/beta (TRA/TRB) single cell RNA sequencing of donor-reactive T cells in stable kidney transplant recipients before and 3-5 years post-transplant.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220956 | GEO | 2023/10/23
REPOSITORIES: GEO
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Project description:Combined transcriptome and T cell receptor alpha/beta (TRA/TRB) single cell RNA sequencing of donor-reactive T cells in stable kidney transplant recipients before and 3-5 years post-transplant.
| PRJNA912159 | ENA
Project description:After kidney transplantation (KT), donor-specific hyporesponsiveness (DSH) of recipient T cells develops over time. Recently, apoptosis was identified as a possible underlying mechanism. In this study, both transcriptomic profiles and complete V(D)J variable regions of TR transcripts from individual alloreactive T cells of kidney transplant recipients were determined with single-cell RNA sequencing. Alloreactive T cells were identified by CD137 expression after stimulation of peripheral blood mononuclear cells obtained from KT recipients (N = 7) prior to and 3-5 years after transplantation with cells of their donor or a third party control. The alloreactive T cells were sorted, sequenced and the transcriptome and T cell receptor profiles were analyzed using unsupervised clustering. Alloreactive T cells retain a highly polyclonal T Cell Receptor Alpha/Beta repertoire over time. Post transplantation, donor-reactive CD4+ T cells had a specific downregulation of genes involved in T cell cytokine-mediated pathways and apoptosis. The CD8+ donor-reactive T cell profile did not change significantly over time. Single-cell expression profiling shows that activated and pro-apoptotic donor-reactive CD4+ T cell clones are preferentially lost after transplantation in stable kidney transplant recipients.
| S-EPMC10572284 | biostudies-literature
Project description:African Americans are at greater risk to reach end-stage renal disease and this risk may carry over in a kidney transplant recipient after kidney transplantation.Linking the five-yr patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 13 692 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function risks were estimated by Cox's regression (hazard ratio [HR] and 95% confidence interval) and logistic regression, respectively.Patients were 48 ± 14 yr old and included 39% women and 26% patients with diabetes. After adjusting for several relevant clinical and transplant-related variables, African American donor race was associated with higher all-cause mortality, with HR of 1.39 (1.09-1.78) for all-cause mortality, 1.80 (1.17-2.76) for cardiovascular mortality, 1.30 (1.03-1.64) for death-censored graft loss and 1.31 (1.10-1.57) for combined outcome over the six-yr observation period. In the non-African American recipient subcohort, but not in the African American recipient subcohort, African American donor race was associated with higher risk of death-censored graft loss (2.24 [1.44-3.49]) in our fully adjusted model.African American donor race was associated with increased all-cause and cardiovascular mortality and graft loss.
| S-EPMC3593049 | biostudies-literature
Project description:Complications due to long-term administration of immunosuppressive therapy increase the morbidity and mortality of liver transplant recipients. Discontinuation of immunosuppressive drugs in recipients spontaneously developing operational tolerance could substantially lessen this burden. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients. Methods. We enrolled 102 stable liver transplant recipients in an immunosuppression withdrawal trial in which drugs were gradually discontinued over a 6-9 month period. Patients with stable graft function and no signs of rejection in a liver biopsy conducted 12 months after cessation of immunosuppressive therapy were considered operationally tolerant. Results. Out of the 98 recipients who completed the study, immunosuppression discontinuation was successful in 41 recipients and rejection occurred in 57. Rejection episodes were mild and were resolved in all cases. Development of tolerance was independently associated with time elapsed since transplantation, recipient age, and male gender. No histological damage was apparent in protocol biopsies performed after successful drug withdrawal.
2012-01-09 | GSE28842 | GEO
Project description:The transmission of cancer from a donor organ is a rare event but has important consequences. Aim of this systematic review was to summarize all the published evidence on cancer transmission in kidney recipients. We reviewed published case reports and series describing the outcome of recipients with donor-transmitted cancer until August 2019. A total of 128 papers were included, representing 234 recipients. The most common transmitted cancers were lymphoma (n = 48, 20.5%), renal cancer (42, 17.9%), melanoma (40, 17.1%), non-small cell lung cancer (n = 13, 5.6%), neuroendocrine cancers comprising small cell lung cancer (n = 11, 4.7%) and choriocarcinoma (n = 10, 4.3%). There was a relative lack of glioblastoma and gastrointestinal cancers with only 6 and 5 cases, respectively. Melanoma and lung cancer had the worst prognosis, with 5-years overall survival of 43% and 19%, respectively; while renal cell cancer and lymphomas had a favorable prognosis with 5-years overall survival of 93 and 63%, respectively. Metastasis of cancer outside the graft was the most important adverse prognostic factor. Overall reporting was good, but information on donors' cause of death and investigations at procurement was often lacking. Epidemiology of transmitted cancer has evolved, thanks to screening with imaging and blood tests, as choriocarcinoma transmission have almost abolished, while melanoma and lymphoma are still difficult to detect and prevent.
| S-EPMC7701067 | biostudies-literature
Project description:BackgroundBK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients.MethodsWe prospectively collected pretransplant plasma and urine samples from living and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G (IgG) testing on pretransplant and serially collected posttransplant samples in kidney transplant recipients.ResultsAmong deceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4% (6/39) of living donors and 8.5% (4/47) of deceased donors of recipients at our institution (P = .50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6% vs 7.8%; P < .001) and viremia (66.6% vs 8.9%; P < .001) with a shorter time to onset (log-rank test, P < .001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pretransplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (P = .31, P = .75, and P = .51, respectively).ConclusionsDonor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at risk for BKV complications.
| S-EPMC6603974 | biostudies-literature
Project description:Allograft tolerance, in which a graft is accepted without long-term immunosuppression, could overcome numerous obstacles in transplantation. Human allograft tolerance has been intentionally induced across HLA barriers via combined kidney and bone marrow transplantation (CKBMT) with a regimen that induces only transient chimerism. Tregs are enriched early after CKBMT. While deletional tolerance contributes to long-term tolerance, the role of Tregs remains unclear. We have optimized a method for identifying the donor-specific Treg repertoire and used it to interrogate the fate of donor-specific Tregs after CKBMT. We expanded Tregs with several different protocols. Using functional analyses and T cell receptor sequencing, we found that expanding sorted Tregs with activated donor B cells identified the broadest Treg repertoire with the greatest potency and donor specificity of suppression. This method outperformed both alloantigen stimulation with CTLA4Ig and sequencing of CFSElo cells from the primary mixed lymphocyte reaction. In 3 tolerant and 1 nontolerant CKBMT recipients, we sequenced donor-specific Tregs before transplant and tracked them after transplant. Preexisting donor-specific Tregs were expanded at 6 months after CKBMT in tolerant patients and were reduced in the nontolerant patient. These results suggest that early expansion of donor-specific Tregs is involved in tolerance induction following CKBMT.
| S-EPMC6302945 | biostudies-literature
Project description:Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ??48-h interval or a relapse of BSIs by the same pathogen at a ??1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR?=?5.31; 95% CI?=?2.27-12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications.
| S-EPMC7577647 | biostudies-literature
Project description:Socioeconomically deprived individuals with renal disease are less likely to receive a live-donor kidney transplant than less-deprived individuals. This qualitative study aimed to identify reasons for the observed socioeconomic disparity in live-donor kidney transplantation.A qualitative study using face-to-face in-depth semistructured interviews.A UK tertiary renal referral hospital and transplant centre.Purposive sampling was used to select deceased-donor transplant recipients from areas of high socioeconomic deprivation (SED) (19 participants), followed by a low SED comparison group (13 participants), aiming for maximum diversity in terms of age, gender, ethnicity, primary renal disease and previous renal replacement therapy.Participants were interviewed following their routine transplant clinic review. Interviews were digitally audio-recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using the constant comparison method described in Grounded Theory.Themes common and distinct to each socioeconomic group emerged. 6 themes appeared to distinguish between individuals from areas of high and low SED. 4 themes were distinct to participants from areas of high SED: (1) Passivity, (2) Disempowerment, (3) Lack of social support and (4) Short-term focus. 2 themes were distinct to the low SED group: (1) Financial concerns and (2) Location of donor.Several of the emerging themes from the high SED individuals relate to an individual's lack of confidence and skill in managing their health and healthcare; themes that are in keeping with low levels of patient activation. Inadequate empowerment of socioeconomically deprived individuals by healthcare practitioners was also described. Financial concerns did not emerge as a barrier from interviews with the high SED group. Interventions aiming to redress the observed socioeconomic inequity should be targeted at both patients and clinical teams to increase empowerment and ensure shared decision-making.
| S-EPMC4785291 | biostudies-other
Project description:Background and objectivesWaiting times to deceased-donor transplantation (DDTx) have significantly increased in the past decade. This trend particularly affects older candidates given a high mortality rate on dialysis.Design, setting, participants, & measurementsWe conducted a retrospective analysis from the national Scientific Registry of Transplant Recipients database that included 54,669 candidates who were older than 60 yr and listed in the United States for a solitary kidney transplant from 1995 through 2007. Using survival models, we estimated time to DDTx and mortality after candidate listing with and without patients initially listed as temporarily inactive (status 7).ResultsAlmost half (46%) of candidates who were older than 60 yr and listed in 2006 through 2007 are projected to die before receiving a DDTx. This proportion varied by individual characteristics: Diabetes (61%), age > or =70 yr (52%), black (62%), blood types O (60%) and B (71%), highly sensitized (68%), and on dialysis at listing (53%). Marked variation also existed by United Network for Organ Sharing region (6 to 81%). The overall projected proportion was reduced to 35% excluding patients who initially were listed as status 7.ConclusionsThese data highlight the prominent and growing challenge facing the field of kidney transplantation. Older candidates are now at significant risk for not surviving the interval in which a deceased-donor transplant would become available. Importantly, this risk is variable within this population, and specific information should be disseminated to patients and caregivers to facilitate informed decision-making and potential incentives to seek living donors.
| S-EPMC2709520 | biostudies-literature