Dataset Information

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection.

ABSTRACT: Early detection of kidney transplant (KT) rejection remains a challenge in patient care. Non-invasive biomarkers hold high potential to detect rejection, adjust immunosuppression, and monitor KT patients. So far, no approach has fully satisfied requirements to innovate routine monitoring of KT patients. In this two-center study we analyzed a total of 380 urine samples. T cells and tubular epithelial cells were quantified in KT patients with graft deterioration using flow cytometry. Epigenetic urine cell quantification was used to confirm flow cytometric results. Moreover, a cohort of KT patients was followed up during the first year after transplantation, tracking cell subsets over time. Abundance of urinary cell counts differed in patients with and without rejection. Most strikingly, various T cell subsets were enriched in patients with T cell-mediated rejection (TCMR) compared to patients without TCMR. Among T cell subsets, CD8+HLA-DR+ T cells were most distinctive (AUC = 0.91, Spec.: 95.9%, Sens.: 76.5%). Epigenetic analysis confirmed T cell and tubular epithelial cell quantities as determined by flow cytometry. Urinary T cell abundance in new KT patients decreased during their first year after transplantation. In conclusion urinary T cells reflect intrarenal inflammation in TCMR. T cell subsets yield high potential to monitor KT patients and detect rejection. Hereby we present a promising biomarker to non-invasively diagnose TCMR.

SUBMITTER: Grothgar E

PROVIDER: S-EPMC9334669 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection.

Grothgar Emil E Goerlich Nina N Samans Bjoern B Skopnik Christopher M CM Metzke Diana D Klocke Jan J Prskalo Luka L Freund Paul P Wagner Leonie L Duerr Michael M Matz Mareen M Olek Sven S Budde Klemens K Paliege Alexander A Enghard Philipp P

Frontiers in medicine 20220715

Early detection of kidney transplant (KT) rejection remains a challenge in patient care. Non-invasive biomarkers hold high potential to detect rejection, adjust immunosuppression, and monitor KT patients. So far, no approach has fully satisfied requirements to innovate routine monitoring of KT patients. In this two-center study we analyzed a total of 380 urine samples. T cells and tubular epithelial cells were quantified in KT patients with graft deterioration using flow cytometry. Epigenetic ur ...[more]

PMID: 35911418

Similar Datasets

Project description:Background and objectivesThe current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.Design, setting, participants, & measurementsUsing data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models.ResultsOf the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).ConclusionsHLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients.

Project description:BackgroundCorrelation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.MethodsWe retrospectively assessed patients with transplant biopsies scored following Banff'15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA.ResultsOne-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31-10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78-16.76], p = 0.003) were independent predictors of ABMRhDSApos.ConclusionsIn conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.

Project description:BackgroundUrine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery.MethodsUrine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection (AR), which were biopsy matched. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Ue) underwent mass spectroscopy-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in AR.ResultsA total of 1018 proteins were identified in Uw and 349 proteins in Ue. Two hundred seventy-nine overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients, 220 had not been previously identified in the normal Ue fraction. Eleven Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with AR, three of which are exclusive to the Ue fraction. Ue AR-specific biomarkers (1) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw.ConclusionA rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue-specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR.

Dataset Information

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection.

Publications

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets