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Donor exchange programs were designed to allocate organs for highly sensitized (HS) patients. The allocation algorithm differs slightly among countries and includes different strategies to improve access to transplants in HS patients. However, many HS patients with a calculated panel reactive of antibodies (cPRA) of 100 % remain on the waiting list for a long time. Some allocation algorithms assume immunological risk, including Imlifidase treatment, to increase the chance of transplantation in very HS patients. Here, we describe our unicenter experience of low-risk delisting strategy in 15 HS patients included in the Spanish donor exchange program without donor offers. After delisting, 7 out of 15 HS patients reduced the cPRA below 99.95 % and impacted the reduction of time on the waiting list (p = 0.01), where 5 out of 7 achieved transplantation. Within those HS that remained above 99.95 %, 1 out of 8 was transplanted. All the HS were transplanted with delisted DSA, and only one with DSA level rebounded early after transplantation. All HS transplanted after delisting maintain graft function. The transplant immunology laboratories are challenged to search intermediate risk assessment methods for delisting high HS patients. [ABSTRACT FROM AUTHOR]

Accurate identification of HLA antibodies using the single antigen bead (SAB) assay is critical for assessment of pre/post-transplant immunological risk and successful virtual crossmatching. Unfortunately, high titer HLA antibodies can be missed or underestimated in the SAB assay as a result of interference with the detection of IgG. This so called prozone effect has been attributed to both complement- and IgM-dependent mechanisms and can be minimized with serum dilution or treatment with heat, EDTA, or DTT. In this study we describe the frequency, nature, and degree of prozone in a cohort of highly sensitized patients (cPRA ≥ 95%), in whom accurate detection of HLA antibodies and virtual crossmatching is of paramount importance. Sera were tested by the SAB assay ± EDTA treatment, ±1:10 dilution to identify the prozone effect. The relative contribution of complement vs IgM to prozone was assessed using anti-C3d and anti-IgM reporter antibodies, respectively. We found that prozone was very frequent in highly sensitized patients (80%), especially those with a history of previous transplantation (87%). Class I HLA specificities were more commonly affected than class II and the susceptibility to prozone was locus dependent with HLA-A(31%), -B(29%) and -DQ(26%) being affected more frequently than HLA-DP(17%), -C(16%) and -DR(5%) antigens. Interestingly, the presence of prozone could be predicted by C3d positivity (MFI ≥ 4000; sensitivity = 95.2%, specificity = 97.2%) and the degree of prozone correlated directly with the extent of C3d deposition. The role of IgM was less clear. However, serum dilution studies suggested that IgM may contribute to interference in a small subset of prozone positive specificities. Our study underscores the importance of serum treatment to inhibit complement activation and minimize prozone in the SAB assay, especially in highly sensitized patients. [ABSTRACT FROM AUTHOR]

This report describes an algorithm for identifying acceptable HLA antigens for highly alloimmunized patients without the need for extensive serum screening. This algorithm is based on the concept that immunogenic epitopes are represented by amino acid triplets on exposed parts of protein sequences of human leukocyte antigen chains (HLA-A, HLA-B, and HLA-C) accessible to alloantibodies. A computer program (HLAMatchmaker) has been developed to determine class I HLA compatibility at the molecular level. It makes intralocus and interlocus comparisons of polymorphic triplets in sequence positions to determine the spectrum of non-shared triplets on donor HLA antigens. In most cases is it possible to identify certain mismatched HLA antigens that share all their polymorphic triplets with the patient’s HLA antigens and could therefore, be considered fully compatible. HLAMatchmaker permits also the identification of additional mismatches that are acceptable as determined from the triplet information on HLA-typed panel cells that do not react with patient’s serum.HLAMatchmaker provides an assessment of donor-recipient HLA compatibility at the structural level and this algorithm is different from conventional methods based on the mere counting of numbers of mismatched HLA antigens or CREGs. This donor selection strategy is suitable especially for allosensitized patients in need of a compatible transplant or platelet transfusion. [Copyright &y& Elsevier]