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To the Editor: Although studies of porcine kidney xenotransplantation in nonhuman primates (NHPs) and brain-dead humans have improved our understanding of anti-xenograft immune responses (1-3), the optimal immunosuppression regimen for [...]

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months postinfection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals. [ABSTRACT FROM AUTHOR]

The feasibility and effectiveness of kidney paired donation (KPD) for the management of patients with incompatible donors were determined. Evidence suggests that recipients with incompatible live donors, even those with rare blood type combinations, can receive transplants through KPD with graft survival rates equivalent to directed, compatible liver donor transplants.

Aim: Use of the virtual crossmatch (XM) has increased the efficiency of organ allocation and reduced the number of organs declined based on unexpected positive XMs (Cecka JM., et al. Am J Transplant. 2011). Despite these benefits, a cell based XM still provides a final safeguard before transplantation. False negative XM predictions may arise when reactivity is due to both antigen specific antibodies and antibodies to crossreactive epitopes. Methods: HLA-specific antibodies were assessed using class I or class II phenotype panels and IgG or C1Q single antigen bead assays. (Lifecodes Immucor; Labscreen, One Lambda,Inc). One wash CDC B cell XMs were performed. Results: Luminex IgG tests yielded reactivity with DR53 phenotypes ranging from 3,000-10,000 MFI with DR53 heterozygotes and >10,000 MFI with homozygotes. Reactivity with DR10 phenotypes were 2,000-3,000 MFI. Single antigen beads yielded reactions with DR53 of 20,000 MFI with undiluted serum and 17,000 MFI with serum diluted 1:8. Reactions with DR10 were 15,000 and 2,000 MFI with undiluted and 1:8 diluted serum, respectively. MFI values given above would predict negative XMs with DR10+/DR53- cells and positive XMs with DR10-/DR53+ cells. The C1q assay yielded MFI values of 28,000 with DR53 and 300 with DR10. These C1Q results substantiate the prediction of a negative CDC XM result with a DR10 cell. CDC XM tests yielded the following results: + with a titer of 2 with a DR10+/DR53- cell, + with a titer of 32 with a DR10-/DR53 homozygote cell, and negative with DR53 heterozygotes and with cells bearing other antigens crossreactive with DR10 (DR1 and DR15/51). Conclusions: We propose that the CDC+ XM with the DR10 cell was due to contributions from the DR10 antibodies and the much stronger antibodies to DR53 that shares one or more epitopes with DR10. These data show that accurate prediction of crossmatches must take into account the possible contributions of antibodies positive for antigens crossreactive with the target antigen. [Copyright &y& Elsevier]

Aim: Interpretation of HLA antibody reactivity should consider different HLA-Bw4 epitopes associated with HLA-B and HLA-A alleles. Methods: HLA typing was performed using Luminex based rSSOP (LAB Type, One Lambda) or sequence based typing (AlleleSEQR, Celera). HLA antibody testing used HLA phenotype (LIFECODES, Gen-Probe) and single antigen (LAT, One Lambda) bead panels on a Luminex platform. Results: Bw4 is an epitope present on several HLA-A and HLA-B antigens that can be divided into 8 subtypes based on amino acid differences (Tissue Ag 2000, 56:363). Recently, residues 80-83 have been shown to influence electrostatic potential of the Bw4 epitope, explaining differences in serological patterns (Human Immunol 2011, 72:1049). We present two patients with Bw4 present in their own phenotype yet they generated antibody to a different Bw4 subtype. Patient 1 typed as a B∗44:03, containing Bw4 residues 80T-81A-82L-83R. She was sensitized through pregnancy to her daughter who typed as a HLA-B∗27:02 containing Bw4 residues 80I-81A-82L-83R. This daughter was a potential HLA mismatched stem cell donor. Patient 2 was a renal patient who typed as a HLA-B∗37:01 containing Bw4 residues 80T-81L-82L-83R. This patient was sensitized to HLA-B51 and -B53, both contain Bw4 residues 80I-81A-82L-83R. Patient 2 is being evaluated for retransplantation. For both patients, the strongest antibody reactivity was toward beads containing the Bw4 motif 80I-81A-82L-83R, to which they were both sensitized. Moreover, there were differences in antibody strength toward HLA antigens that differed only by the 80I-81A-82L-83R epitope (B49 vs B50 and B38 vs B39). Cell adsorptions are underway to confirm the presence of Bw4 subtype-specific antibodies. Conclusions: Sensitization to Bw4 subtypes may be relevant when selecting HLA allele mismatched donors for antigens that contain multiple Bw4 subtypes. Accurate characterization of antibody specificity permits identification of incompatible alleles not represented on HLA bead panels. [Copyright &y& Elsevier]