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Volume 86, Issue 5, Pages (November 2014)

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Presentation on theme: "Volume 86, Issue 5, Pages (November 2014)"— Presentation transcript:

1 Volume 86, Issue 5, Pages 1039-1048 (November 2014)
Impact of donor mismatches at individual HLA-A, -B, -C, -DR, and -DQ loci on the development of HLA-specific antibodies in patients listed for repeat renal transplantation  Vasilios Kosmoliaptsis, Olivera Gjorgjimajkoska, Linda D. Sharples, Afzal N. Chaudhry, Nikolaos Chatzizacharias, Sarah Peacock, Nicholas Torpey, Eleanor M. Bolton, Craig J. Taylor, J. Andrew Bradley  Kidney International  Volume 86, Issue 5, Pages (November 2014) DOI: /ki Copyright © 2014 International Society of Nephrology Terms and Conditions

2 Figure 1 Association between first transplant human leukocyte antigen (HLA) class I (HLA-A, -B, and -C) mismatches and HLA-specific sensitization expressed as calculated reaction frequency (cRF). HLA class I–specific alloantibodies were detected using single-antigen HLA beads (with a median fluorescence intensity (MFI) cutoff threshold of 2000); the likelihood of identifying an antibody-compatible organ donor (cRF) was determined by comparing individual patient HLA-specific antibody profiles with the HLA types of 10,000 consecutive UK deceased organ donors. Panel (a) shows cRF levels attributable to antibodies against HLA-A, -B, and -C considered collectively according to the total number of donor–recipient HLA-A, -B, and -C mismatches (0–6) at the three different time points: pretransplant, on return to the transplant waiting list, and at peak cRF while on the waiting list. Panels (b–d) show the cRF attributable to antibodies against HLA-A, HLA-B, and HLA-C, respectively, according to the number of HLA specificities (0, 1, or 2) mismatched at the individual HLA loci. Patients were categorized according to the likelihood of identifying an antibody-compatible organ donor as cRF 0–15%, cRF 16–50%, cRF 51–84%, and cRF 85–100%. cRF levels attributable to antibodies against each of the HLA class I loci and for HLA class I loci considered collectively increased between the three different time points (Stuart–Maxwell test P<0.01), with the exception of the comparison between pretransplant and return to the transplant waiting list for HLA-C (P=0.427). The number of patients within each cRF category at the three different time points is depicted in Supplementary Table S1A online stratified according to the number of HLA mismatches. Kidney International  , DOI: ( /ki ) Copyright © 2014 International Society of Nephrology Terms and Conditions

3 Figure 2 Association between first transplant human leukocyte antigen (HLA) class II (HLA-DRB1, -DRB3/4/5, and -DQ) mismatches and HLA-specific sensitization expressed as calculated reaction frequency (cRF). HLA class II–specific alloantibodies were detected using single-antigen HLA beads (with a median fluorescence intensity (MFI) cutoff threshold of 2000); donor organ incompatibility (cRF) was determined by comparing individual patient HLA-specific antibody profiles with the HLA types of 10,000 consecutive UK deceased organ donors. Panel (a) shows cRF levels attributable to antibodies against HLA-DRB1, -DRB3/4/5, and -DQ considered collectively, according to the total number of donor–recipient HLA-DRB1, -DRB3/4/5, and -DQ mismatches (0–6) at the three different time points: pretransplant, on return to the transplant waiting list and at peak cRF while on the waiting list. Panels (b–d) show the cRF attributable to antibodies against HLA-DRB1, HLA-DRB3/4/5, and HLA-DQ, respectively, according to the number of HLA specificities (0, 1, or 2) mismatched at the individual HLA loci. Patients were categorized according to the likelihood of identifying an antibody-compatible organ donor as cRF 0–15%, cRF 16–50%, cRF 51–84%, and cRF 85–100%. cRF levels attributable to antibodies against each of the HLA class II loci and for HLA class II loci considered collectively increased between the three different time points (Stuart–Maxwell test P<0.01). The number of patients within each cRF category at the three different time points is depicted in Supplementary Table S1A online stratified according to the number of HLA mismatches. Kidney International  , DOI: ( /ki ) Copyright © 2014 International Society of Nephrology Terms and Conditions

4 Figure 3 Association between first transplant human leukocyte antigen (HLA) class I and II mismatches and peak HLA-specific sensitization according to different levels (median fluorescence intensity (MFI)) of circulating alloantibodies. HLA-specific alloantibodies were identified in sera from patients re-listed for repeat transplantation, using HLA single-antigen beads. Donor organ incompatibility (calculated reaction frequency (cRF)) was determined by comparing individual patient HLA-specific antibody profiles with the HLA types of 10,000 consecutive UK deceased organ donors. The figure shows cRF levels in peak reactive sera attributable to antibodies against HLA-A, -B, -C, -DRB1, -DRB3/4/5, and -DQ considered collectively, according to the total number of first transplant donor HLA mismatches (0–12). Alloantibodies were analyzed at the three different MFI cutoff thresholds (2000, 5000, and 8000), where alloantibodies present at increasing thresholds indicate increasing immunological risk for repeat kidney transplantation. Patients were categorized according to the likelihood of identifying an antibody-compatible organ donor as cRF 0–15%, cRF 16–50%, cRF 51–84%, and cRF 85–100%. The number of patients within each cRF category is depicted in Supplementary Table S1B online stratified according to the number of HLA class I and class II mismatches. Kidney International  , DOI: ( /ki ) Copyright © 2014 International Society of Nephrology Terms and Conditions


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