IMPACT OF REPEAT HLA MISMATCHES ON KIDNEY GRAFT SURVIVAL: A CONTEMPORARY COLLABORATIVE TRANSPLANT STUDY (CTS) ANALYSIS.

Repeat HLA mismatches (RMM) have been historically associated with an increased risk of graft loss after repeat kidney transplantation, in particular HLA-DR RMM in sensitized recipients. As routine use of sensitive assays can at present prevent the transplantation of RMM in hosts with donor-specific antibodies, we hypothesized that RMM would no longer be associated with graft loss. We performed a registry analysis of the Collaborative Transplant Study database including 6711 patients who received a second kidney transplant (2 KT) between 2010 and 2021, with at least one HLA-A, -B or -DR mismatch.

Personalized treatment supported by automated quantitative fluid analysis in active neovascular age-related macular degeneration (nAMD)-a phase III, prospective, multicentre, randomized study: design and methods.

Introduction: In neovascular age-related macular degeneration (nAMD) the exact amount of fluid and its location on optical coherence tomography (OCT) have been defined as crucial biomarkers for disease activity and therapeutic decisions. Yet in the absence of quantitative evaluation tools, real-world care outcomes are disappointing. Artificial intelligence (AI) offers a practical option for clinicians to enhance point-of-care management by analysing OCT volumes in a short time.

Rare Malignant Indications for Liver Transplantation: A Collaborative Transplant Study Report.

Hepatocellular carcinoma (HCC) is by far the leading malignant indication for liver transplantation (LT). Few other malignancies, including cholangiocellular carcinoma (CCC), metastases from neuroendocrine tumors (NET), and sarcomas of the liver (LSAR), also are commonly accepted indications for LT. However, there is limited information on their outcome after LT.

Outcome of Extended Right Lobe Liver Transplantations.

Split-liver transplantation offers a solution to the organ shortage problem. However, the outcomes of extended right lobe liver transplantation (ERLT) and whether it is a suitable alternative to full-size liver transplantation (FSLT) remain controversial. We compared the outcomes of ERLT and FSLT in adult recipients of 43,409 first deceased donor liver transplantations using Cox regression.

Analysis of de novo donor-specific HLA-DPB1 antibodies in kidney transplantation.

HLA matching and avoidance of unacceptable mismatches are important aspects in the selection of donors for solid organ transplantation. The impact of HLA-DPB1 incompatibility on the outcomes of kidney transplantation is not fully understood. We investigated a potential effect of mismatching for HLA-DPB1 at allele, eplet, or Terasaki epitope (TerEp) level on the formation of de novo donor-specific antibodies (dnDSA) and also asked whether polymorphisms associated with HLA-DPB1 expression level may influence dnDSA induction.

Can PIRCHE-II Matching Outmatch Traditional HLA Matching?

We analyzed in a cohort of 68,606 first deceased donor kidney transplantations reported to the Collaborative Transplant Study whether an epitope-based matching of donor-recipient pairs using the Predicted Indirectly ReCognizable HLA Epitopes algorithm (PIRCHE-II) is superior to currently applied HLA antigen matching. PIRCHE-II scores were calculated based on split antigen HLA-A, -B, -DRB1 typing and adjusted to the 0-6 range of HLA mismatches. PIRCHE-II scores correlated strongly with the number of HLA mismatches (Spearman ρ = 0.

Should kidney allografts from old donors be allocated only to old recipients?

In several deceased donor kidney allocation systems, organs from elderly donors are allocated primarily to elderly recipients. The Eurotransplant Senior Program (ESP) was implemented in 1999, and since then, especially in Europe, the use of organs from elderly donors has steadily increased. The proportion of ≥60-year-old donors reported to the Collaborative Transplant Study (CTS) by European centers has doubled, from 21% in 2000-2001 to 42% in 2016-2017.

Critical evaluation of a possible role of HLA epitope matching in kidney transplantation.

Human leukocyte antigen (HLA) matching is one of the cornerstones of organ allocation in deceased-donor kidney transplantation. Increased numbers of HLA allele mismatches are associated with a higher risk of immunological rejection, de novo donor-specific HLA antibody development and graft failure. HLA epitopes are defined as the specific portions of HLA molecules to which antibodies and T-cell receptors bind with their paratopes.

Hematopoietic-Extrinsic Cues Dictate Circadian Redistribution of Mature and Immature Hematopoietic Cells in Blood and Spleen.

Circadian oscillations in circulating leukocyte subsets including immature hematopoietic cells have been appreciated; the origin and nature of these alterations remain elusive. Our analysis of wild-type C57BL/6 mice under constant darkness confirmed circadian fluctuations of circulating leukocytes and clonogenic cells in blood and spleen but not bone marrow. Clock gene deficient - mice lacked this regulation.

Relevance of donor-specific antibody monitoring after kidney transplantation: Findings from the Collaborative Transplant Study and the Heidelberg Transplant Center.

Monitoring of donor-specific HLA antibodies (DSA) has become part of the clinical routine in kidney transplantation. This paper gives a brief overview on data from the Collaborative Transplant Study (CTS) and the Heidelberg Transplant Center on the clinical relevance of post-transplant DSA monitoring in patients undergoing renal transplantation. The obtained findings underline the importance of DSA monitoring in the post-operative course in immunologically high-risk patients and patients with deterioration of graft function.

Progressive improvement in short-, medium- and long-term graft survival in kidney transplantation patients in Ireland - a retrospective study.

It is often quoted that while short-term graft survival in kidney transplantation has improved in recent years, it has not translated into a commensurate improvement in long-term graft survival. We considered whether this was true of the entire experience of the national kidney transplant program in Ireland. A retrospective analysis of the National Kidney Transplant Service (NKTS) database was undertaken to investigate patient and graft survival for all adult first deceased donor kidney transplant recipients in Ireland, 1971-2015.

Pretransplant Cancer in Kidney Recipients in Relation to Recurrent and De Novo Cancer Incidence Posttransplantation and Implications for Graft and Patient Survival.

Background: Whether kidney transplant recipients who were treated for a malignant tumor before transplantation are at an increased risk of developing a tumor posttransplantation has not been adequately quantified and characterized.

Methods: We studied more than 270 000 patients on whom pretransplant and posttransplant malignancy data were reported to the Collaborative Transplant Study. More than 4000 of these patients were treated for pretransplant malignancy.

Correction: Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

[This corrects the article DOI: 10.1371/journal.pone.

Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

Background: There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient.

IFNy+ and IFNy- Treg subsets with stable and unstable Foxp3 expression in kidney transplant recipients with good long-term graft function.

Background: Treg are a heterogenous cell population. In the present study we attempted to identify Treg subsets that might contribute to stable and good long-term graft function.

Method: Lymphocyte and Treg subsets were studied in 136 kidney transplant recipients with good long-term graft function and in 52 healthy control individuals using eight-color-fluorescence flow cytometry.

Efficacy and safety of antibody induction therapy in the current era of kidney transplantation.

Background: Antibody induction with polyclonal rabbit-antithymocyte globulin (rATG) or an interleukin-2 receptor antagonist (IL-2RA) is widely used in kidney transplantation.

Methods: Collaborative Transplant Study data from 38 311 first deceased-donor kidney transplants (2004-13) were analysed. Transplants were classified as 'normal risk' or 'increased risk' according to current guidelines.

Immunosuppression with mammalian target of rapamycin inhibitor and incidence of post-transplant cancer in kidney transplant recipients.

Background: Evidence is limited regarding the effect of de novo therapy with mammalian target of rapamycin (mTOR) inhibitors on cancer risk after kidney transplantation.

Methods: Collaborative Transplant Study data from 78 146 adult recipients of first deceased-donor kidney transplants (1999-2013) were analysed (4279 mTOR inhibitor, 73 867 no mTOR inhibitor) using standard methods. Propensity score matching was performed for analysis of basal cell and squamous cell skin cancer.

The collaborative transplant study registry.

The Collaborative Transplant Study (CTS) was initiated in 1982. Over the last 30 years, it has collected information on over half a million kidney, liver, heart, lung, and pancreas transplant procedures. Participation is voluntary and the study has strictly scientific objectives.

Deleterious impact of HLA-DRB1 allele mismatch in sensitized recipients of kidney retransplants.

Background: Whether mismatches between donor and recipient of a kidney transplant at the HLA allele level can elicit an immune response strong enough to impact graft survival is not known.

Methods: We examined the influence of HLA-DRB1 allele level mismatch on graft survival based on high-resolution typing, utilizing blood samples and clinical data provided by the Collaborative Transplant Study. HLA-DRB1*04 was selected as a model for this investigation because it is the most common HLA-DRB1 allele group and consists of several alleles with relatively high frequencies, allowing for analysis of transplants matched at the antigen level but mismatched at the allele level.