Virtual crossmatch

BACKGROUND: While there is increasing reliance on a negative virtual crossmatch to proceed with deceased donor kidney transplantation, a flow cytometry crossmatch (FCXM) is still usually performed after the transplant has already occurred. Our center has eliminated pretransplant physical crossmatches for most patients, and since 2018, we have eliminated the systematic performance of posttransplant FCXMs. METHODS: We studied all deceased donor kidney transplants in our program between June 1, 2018, and March 31, 2021, to evaluate the impact of eliminating retrospective FCXMs on resource utilization and graft outcomes (ie, the occurrence of antibody-mediated rejection [AMR] in the first 3-mo posttransplant)...

Precise typing of human leukocyte antigens (HLA) is crucial for clinical hematopoietic stem cell and solid organ transplantations, transfusion medicine, HLA-related disease association, and drug hypersensitivity analysis. The UCLA Cell Exchange program has played a vital role in providing educational and proficiency testing surveys to HLA laboratories worldwide for the past 5 decades. This article highlights the significant contribution of the UCLA Cell and DNA Exchange Programs in advancing HLA antibody testing, genotyping, crossmatches, and, more recently, virtual crossmatches...

BACKGROUND: Solid organ transplantation is a life-saving medical operation that has progressed greatly because of developments in diagnostic tools and histocompatibility tests. Crossmatching for complement-dependent cytotoxicity (CDC) and human leukocyte antigen (HLA) typing are two important methods for checking graft compatibility and reducing the risk of graft rejection. HLA typing and CDC crossmatching are critical in kidney, heart, lung, liver, pancreas, intestine, and multi-organ transplantation...

The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the guidance of induction protocols and treatment with immunosuppressants. The crossmatch tests in transplantation can be physical or virtual, each with its advantages and limitations. Currently, the virtual crossmatch stands out for its sensitivity and specificity compared to the physical tests. Additionally, the virtual crossmatch can be performed in less time, allowing for a reduction in cold ischemia time...

Complement-dependent cytotoxicity crossmatch (CDC-XM) has been considered for many years the standard of practice for determining compatibility in solid organ transplantation (SOT). However, as this method is laborious, time intensive and lacks sensitivity and specificity, it has been replaced in many laboratories worldwide by flow cytometry crossmatch (FCXM) and/or virtual crossmatch (vXM). With this study we intend to show the relevance of performing CDC-XM in the era of virtual crossmatching. We retrospectively analyzed 1,007 consecutive T and B cell deceased donor (DD) CDC-XMs performed in parallel using non-treated and dithiothreitol (DTT) treated sera between May 2022 and January 2023 in waitlisted patients with no donor specific antibodies (DSA) against HLA-A, B and/or DR antigens...

Pretransplant immunological assessment of a transplant donor has evolved significantly over the last few decades with the advent of testing platforms with enhanced sensitivity and varying formats. The single antigen bead assay (SAB) assay, a virtual crossmatch (vXM) is used extensively and considered the gold standard for defining donor-specific antibodies (DSA) in many parts of the World. A country like India, is however challenged by the lack of adequate representation of locally frequent HLA alleles and hence in our institution, we continue to perform a physical crossmatch (pXM) on the Complement Dependent Cytotoxicity and flow cytometry platforms alongside the SAB...

Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results...

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018...

Proficiency testing (PT) surveys include data from laboratories across the world and are ideal for creating advanced educational content, beyond just consensus grading. Educational challenges provide a unique opportunity to probe common laboratory practices and risk assessment, especially in cases where there is no "analyte" tested. Human leukocyte antigen (HLA) compatibility evaluation between donor and recipient pairs has been traditionally assessed using T-cell and B-cell physical crossmatches. However, advancements in our ability to identify and characterize HLA antibodies using solid phase assays, in combination with changing deceased donor allocation schemes and improved HLA typing, have shifted the paradigm from performing physical crossmatches to the use of the virtual crossmatch (VXM)...

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Recent studies showed that ABO-adjusted calculated panel reactive antibody (ABO-cPRA) may better reflect the histocompatibility level in a multi-ethnic population, but such data in Asians is not available. We developed an ABO-adjusted cPRA metric on a cohort of waitlist kidney transplant patients (n = 647, 99% Chinese) in Hong Kong, based on HLA alleles and ABO frequencies of local donors. The concordance between the web-based ABO-cPRA calculator and the impact on kidney allocation were evaluated...

Imlifidase recently received early access authorization for highly sensitized adult kidney transplant candidates with a positive crossmatch against an ABO-compatible deceased donor. These French consensus guidelines have been generated by an expert working group, in order to homogenize patient selection, associated treatments and follow-up. This initiative is part of an international effort to analyze properly the benefits and tolerance of this new costly treatment in real-life. Eligible patients must meet the following screening criteria: cPRA ≥ 98%, ≤ 65-year of age, ≥ 3 years on the waiting list, and a low risk of biopsy-related complications...

Imlifidase, derived from a Streptococcus pyogenes enzyme, cleaves the entire immunoglobulin G pool within hours after administration in fully cleaved antigen-binding and crystallizable fragments. These cleaved fragments can no longer exert their antibody-dependent cytotoxic functions, thereby creating a window to permit HLA-incompatible kidney transplantation. Imlifidase is labeled, in Europe only, for deceased donor kidney transplantation in highly sensitized patients, whose chances for an HLA-compatible transplant are negligible...

Pronase treatment of lymphocytes has been used to improve the specificity and sensitivity of flow cytometric crossmatch, especially B-cell flow cytometric crossmatch, due to the presence of Fc receptors on the cell surface. Some limitations have been reported in the literature: false negatives due to the reduction of major histocompatibility complex expression and false-positive T cells in HIV+ patients due to exposure to cryptic epitopes. This study aimed to evaluate the effect of pronase in our assays, using untreated and treated cells with 2...

Our program previously reported successful outcomes following virtual crossmatch (VXM)-positive lung transplants managed with peri-operative desensitization, but our ability to stratify their immunologic risk was limited without flow-cytometry crossmatch (FCXM) data before 2014. The aim of this study was to determine allograft and chronic lung allograft dysfunction (CLAD)-free survival following VXM-positive/FCXM-positive lung transplants, which are performed at a minority of programs due to the high immunologic risk and lack of data on outcomes1 ...

Waitlisted sensitised transplant recipients with HLA allele level antibodies to their own HLA antigen family are disadvantaged by current deficiencies in HLA typing for deceased donors. This is primarily because at time of organ allocation, HLA typing is provided at antigen level whereas solid phase assays provide allele level antibody definition. The gold standard for HLA allele typing is next generation sequencing (NGS), however time limitations with established NGS systems prevent NGS use for deceased donors...

The "virtual" crossmatch (VXM) has become a critical tool to predict the compatibility between an organ donor and a potential recipient. Yet, nonstandardized laboratory practice can lead to variability in VXM interpretation. Therefore, UCLA's VXM Exchange survey was designed to understand factors that influence the variability of VXM prediction in the presence of HLA donor-specific antibody (DSA). Thirty-six donor blood samples and 72 HLA reference sera were sent to 35 participating laboratories to perform HLA antibody testing, flow crossmatch (FXM), and VXM from 2014 to 2019, consisting of 144 T/B-cell FXM pairs and 112 T/B-cell VXM pairs...

Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6...

INTRODUCTION: The CDC crossmatch test is being phased out in solid organ donor allocation, and standard luminex single antigen bead assays do not differentiate complement activating function of HLA antibodies. The current study investigated the LIFECODES C3d-binding assay to determine if it could accurately predict actual T and B cell CDC results in a cohort of highly sensitised patients. METHOD: 19 serum samples from different highly sensitised solid organ patients were crossmatched against cells from 62 unique donors, with 174 total T and B cell crossmatches performed...