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Patients listed for renal transplant derive a CPRA from the HLA antibody (Ab) specificities present in patient sera. Unacceptable antigens (UAgs) are identified using the mean fluorescence intensity (MFI) of the patient’s HLA Ab specificity. Each center has an MFI cut-off for UAgs. However, another...

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Bibliographic Details
Published in:Human immunology 2014-10, Vol.75, p.41-41
Main Authors: Jindra, Peter, Saltarrelli, Jerome, O’Mahony, Christine, Buren, Charles Van, McKissick, Eva, Acorda, Noriel, Eaton, Alfred, Woolley, Nicholas, Erice, Phillip, Hoover, Angela, Hollingsworth, Clair, Chappelle, John, Kerman, Ronald
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Language:English
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Summary:Patients listed for renal transplant derive a CPRA from the HLA antibody (Ab) specificities present in patient sera. Unacceptable antigens (UAgs) are identified using the mean fluorescence intensity (MFI) of the patient’s HLA Ab specificity. Each center has an MFI cut-off for UAgs. However, another way to identify UAgs is to use the concentration or titer of the Ab specificity. We studied 21 sera of potential recipients. PRAs, HLA Ab specificities and specificity titers were done using One Lambda, Inc. reagents. The presence of cI/cII HLA Ab specificities was determined in high and low PRA sera and the MFIs of Ab specificities were compared at neat, 1:8 and 1:16 titers. The MFIs of 2523 ± 520 vs 2,647 ± 983 of cI HLA Ab specificities present in neat but gone at a 1:8 serum titer were similar in both low and high PRA sera (34 ± 17% vs 98 ± 3%, p < 0.01). The MFIs of eliminated cI UAgs gone at 1:16 were higher than those MFIs eliminated at 1:8 (6261 ± 2656 vs 2622 ± 752, p < 0.02). Those cI HLA specificities gone at a 1:32 titer had even higher MFIs than the MFIs of specificities gone at 1:16 (8363 ± 3325 vs 6261 ± 2656, p < 0.01). The MFIs of specificities still present at 1:32 were even higher than the MFIs gone at 1:32 (12,532 ± 3606 vs 8363 ± 3325, p < 0.01). The same data were seen for cII UAgs. These data are relevant because we had 54 patients with donor specific antibody (DSA) titers of ⩽1:16. 81% (44/54) of these patients had negative cytotoxic (AHG) and flow cytometric crossmatches (FCXMS) and 19% (10/54) displayed a negative AHG but a positive FCXM. The two year graft survival of the low titer, DSA positive but XM negative patients was 91% vs 60% for the DSA positive, XM positive recipients ( p < 0.01). The data suggests that while the presence of DSA at low titer (⩽1:16) may yield a positive virtual XM the actual XM can be negative. MFI and PRA did not correlate to UAgs that were eliminated with titration. More importantly, UAgs present in neat sera may be eliminated after serum titrations. By only identifying UAgs in neat sera we do not take into account that some UAgs may have a low Ab concentration and may not be clinically deleterious. Since we have data suggesting good clinical transplant outcome in the presence of low titer DSA it may be of benefit to use specificity titration studies to identify UAg specificities.
ISSN:0198-8859
DOI:10.1016/j.humimm.2014.08.051