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In lung transplant recipients, the presence of pretransplant anti-HLA antibodies and/or donor-specific antibodies (MFI > 1000), together with a negative CDC crossmatch, is not associated with a worse chronic lung allograft dysfunction or CLAD-related death in spite of a higher incidence of antibody-mediated rejection.

Technological advances in the field of histocompatibility have allowed us to define anti-HLA antibody specificity to the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6,726 consecutive serum samples from 2,953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation. Out of 17 class I HLA antigens represented by more than one allele in LABScreen Single Antigen Bead (SAB) assay, 12 had potential allele-specific reactivity. Taking advantage of our unbiased cohort of deceased donor-candidate testing (123,135 complement-dependent cytotoxicity (CDC) crossmatches between 2014-2017), we estimated that the presence of allele-specific antibody detected by SAB (MFI >3,000) against only the rare allele was a poor predictor of positive CDC crossmatch, with positive predictive value of 0-7%, compared with 52.5% in allele-concordant class I HLA antibodies against A or B locus antigens. Further, we confirmed allele-specific reactivity using flow crossmatch in three scenarios: A11:01/A11:02, A68:01/A68:02, and B44:02/B44:03. Our results suggest that allele-specific antibodies may unnecessarily exclude transplant candidates (up to 10%) from organ offers by overcalling unacceptable antigens; incorporation of selective reactivity pattern in allocation may promote precision matching and more equitable allocation.

Patients were entered into a randomized trial of prophylaxis for renal allograft rejection by the administration of an anti—human IL-2 receptor antibody, anti-Tac, during the first ten days posttransplant. Interleukin-2 receptor (IL-2 R) expression was measured using two anti-IL-2 R monoclonal antibodies (moAbs), anti-Tac and 1HT4–4H3. These two antibodies recognize closely spaced epitopes on the 55 kD chain of the IL-2 R. IL-2 R expression was examined on peripheral blood small lymphocytes in three groups of patients who received: (A) cyclosporine CsA and prednisone for baseline immunosuppression (n=9); (B) anti-Tac with CsA and prednisone as baseline immunosuppression (n=12); and (C) anti-Tac with azathioprine and prednisone as baseline immunosuppression (n=5). We found that large numbers of T cells express IL-2 receptors despite the presence of anti-Tac (average of IL-2 R—positive cells at day of peak IL-2 R expression 56.0±20.8 in group A, 65.2±26.6 in group B, 21.0± 7.4 in group C). IL-2 R expression did not correlate with clinical activity, and the presence or accessibility of epitopes on the same 55 kD chain varied dramatically from patient to patient.