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This article explores the significance of proficiency testing (PT) in the field of histocompatibility and immunogenetics, particularly in relation to laboratory procedures for organ transplantation. It discusses the historical development of PT and its role in ensuring reliable results for diagnostic work. The article also highlights the evolution of PT methods, including the use of digital data input, and emphasizes the importance of accreditation and certification. It suggests that PT organizers should focus on establishing PTs for defining unacceptable HLA antigens, which are crucial for virtual crossmatching procedures. Additionally, the article emphasizes the need for electronic data storage and analysis to prevent errors, and the importance of using PT reports for accreditation purposes. Finally, it underscores the importance of keeping PT costs low and using PT exercises for reimbursement from medical insurance bodies. [Extracted from the article]

Summary: The Banff antibody‐mediated rejection (ABMR) classification is vulnerable to misinterpretation, but the reasons are unclear. To better understand this vulnerability, we evaluated how ABMR is diagnosed in practice. To do this, the Banff Antibody‐Mediated Injury Workgroup electronically surveyed an international cohort of nephrologists/surgeons (n = 133) and renal pathologists (n = 99). Most providers (97%) responded that they use the Banff ABMR classification at least sometimes, but DSA information is often not readily available. Only 41.1% (55/133) of nephrologists/surgeons and 19.2% (19/99) of pathologists reported that they always have DSA results when the biopsy is available. Additionally, only 19.6% (26/133) of nephrologists/surgeons responded that non‐HLA antibody or molecular transcripts are obtained when ABMR histologic features are present but DSA is undetected. Several respondents agreed that histologic features concerning for ABMR in the absence of DSA and/or C4d are not well accounted for in the current classification [31.3% (31/99) pathologists and 37.6% (50/133) nephrologist/surgeons]. The Banff ABMR classification appears widely accepted, but efforts to improve the accessibility of DSA information for the multidisciplinary care team are needed. Further clarity is also needed in Banff ABMR nomenclature to account for the spectrum of ABMR and for histologic features suspicious for ABMR when DSA is absent. [ABSTRACT FROM AUTHOR]

Summary: The outcomes of lymphocyte‐depleting antibody induction therapy (LDAIT), [thymoglobulin (ATG) or alemtuzumab (ALM)] versus interleukin‐2 receptor antagonist (IL‐2RA) in the nonbroadly‐sensitized [pretransplant calculated panel reactive antibody (cPRA), <80%] adult deceased donor kidney transplant recipients (adult‐DDKTRs) are understudied. In this registry, study of 55 593 adult‐DD‐KTRs, outcomes of LDAIT [(ATG, N = 32 985) and (ALM, N = 9429)], and IL‐2RA (N = 13 179) in <10% and 10–79% cPRA groups was analyzed. Adjusted odds ratio (aOR) of one‐year biopsy‐proven acute rejection (BPAR) was lower; while, aOR of 1‐year composite of re‐hospitalization, graft loss, or death was higher with LDAIT than IL2‐RA in both cPRA groups. Adjusted odds ratio (aOR) of delayed graft function was higher with LDAIT than IL‐2RA in the <10% cPRA group. Adjusted hazard ratio (aHR) of 5‐year death‐censored graft loss (DCGL) in both <80% cPRA groups seemed higher with ALM than other inductions [(<10% cPRA: ALM versus IL2RA, aHR = 1.11, 95% CI = 1.00–1.23 and ATG versus ALM: aHR = 0.84, 95% CI = 0.77–0.91; 10–79% cPRA: ALM versus IL2RA, aHR = 1.29, 95% CI = 1.02–1.64; and ATG versus ALM, aHR = 0.83, 95% CI = 0.70–0.98)]. Five‐year aHR of death did not differ among induction therapies in both cPRA groups. In nonbroadly sensitized adult‐DDKTRs, LDAIT is more protective against 1‐year BPAR (not 5‐year mortality) than IL‐2RA; the trend of a higher 5‐year DCGL risk with ALM than ATG or IL‐2RA needs further investigation. [ABSTRACT FROM AUTHOR]

Summary: We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor‐specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death‐censored allograft loss were assessed by Cox proportional modeling. Death‐censored allograft survival was 77.0% (87/113) during a median follow‐up of 2.2 (IQR 1.2–3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6–15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1–13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post‐transplant (years) until donor‐specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody‐mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA. [ABSTRACT FROM AUTHOR]

Summary: Chronic‐active antibody‐mediated rejection (c‐aABMR) is defined as histological evidence of chronic endothelial injury (cg), also known as transplant glomerulopathy, and either microvascular inflammation (MVI) or positivity for C4d. Importantly, the presence of donor‐specific antibodies (DSA) is currently still mandatory for the diagnosis of c‐aABMR. This retrospective study of 41 c‐aABMR patients investigates whether cases suspicious for c‐aABMR (DSA negative, n = 24) differ from cases of c‐aABMR (DSA positive, n = 17) with respect to renal histology, allograft function and long‐term graft survival. All included patients had progressive loss of allograft function and were diagnosed by for cause biopsy and scored according to the Banff ’15 criteria. In all DSApos cases, DSA were de novo and the majority was directed against HLA‐II being mostly anti‐HLA‐DQ antibodies. There were no statistically significant differences in clinical characteristics, decline in allograft function and renal allograft survival in cases with or without DSAs. All cases showed chronic histomorphological damage and inflammation, irrespective of the presence of DSA. Renal histology and clinical outcome of patients suspicious for c‐aABMR (DSAneg) do not significantly differ from patients with a diagnosis of c‐aABMR (DSApos). We believe that our study adds to the ongoing debate regarding the need for DSAs to be present for the diagnosis of c‐aABMR. [ABSTRACT FROM AUTHOR]

Summary: While advances in patient care and immunosuppressive pharmacotherapies have increased the lifespan of heart allograft recipients, there are still significant comorbidities post‐transplantation and 5‐year survival rates are still significant, at approximately 70%. The last decade has seen massive strides in genomics and other omics fields, including transcriptomics, with many of these advances now starting to impact heart transplant clinical care. This review summarizes a number of the key advances in genomics which are relevant for heart transplant outcomes, and we highlight the translational potential that such knowledge may bring to patient care within the next decade. [ABSTRACT FROM AUTHOR]

The introduction of new sensitive assays for the detection of HLA antibodies on basis of their binding to isolated HLA molecules has got an enormous impact on the decision-making process with respect to donor selection for sensitized patients. In the past, when only complement-dependent cytotoxicity was used as a tool to define HLA alloantibodies, the presence of donor specific antibodies (DSA) before transplantation was considered a contraindication for renal transplantation with that donor. The interpretation of the current DSA results is far more difficult and leads to a lot of discussions and controversy. The problems associated with the use of solid phase assays for clinical decision making and possible solutions are discussed. [ABSTRACT FROM AUTHOR]