Increased Negative Impact of Donor HLA-Specific Together With Non-HLA–Specific Antibodies on Graft Outcome

Reinsmoen, Nancy L.; Lai, Chih Hung; Mirocha, James; Cao, Kai; Ong, Geraldine; Naim, Mehrnoush; Wang, Qi; Haas, Mark; Rafiei, M.; Czer, L.; Patel, Jignesh; Kobashigawa, Jon A.

doi:10.1097/01.tp.0000436927.08026.a8

Cited by 109 publications

(78 citation statements)

References 47 publications

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“…[32][33][34][35][36] We also reported an increased negative impact of antibodies to angiotensin type 1 receptor along with de novo donor HLA specific antibody on heart allograft outcome. 37 There is increasing evidence that antibodies to HLA and non-HLA work in concert toward an increased negative impact on graft dysfunction. [37][38][39][40] In conclusion, we have developed an algorithm to prioritize the assignment of UAs allowing sensitized patients to receive transplants at a rate higher than on the national waitlist.…”

Section: Discussionmentioning

confidence: 99%

“…37 There is increasing evidence that antibodies to HLA and non-HLA work in concert toward an increased negative impact on graft dysfunction. [37][38][39][40] In conclusion, we have developed an algorithm to prioritize the assignment of UAs allowing sensitized patients to receive transplants at a rate higher than on the national waitlist. The outcomes show some increased negative impact on freedom from rejection (AMR and CMR) depending on the pre-transplant status of DSA and crossmatch positivity.…”

Section: Discussionmentioning

confidence: 99%

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Optimizing transplantation of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens

Reinsmoen

Patel²,

Mirocha

et al. 2016

The Journal of Heart and Lung Transplantation

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Optimizing transplantation of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens

Reinsmoen

Patel²,

Mirocha

et al. 2016

The Journal of Heart and Lung Transplantation

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“…With regards that the detection of HLA and non-HLA antibodies specific to donor (DSA) is critical finding to predict alloimmune response to kidney allograft, particularly antibody mediated rejection (AMR) (12)(13)(14), understanding the significance of various aspects of each test and utilization of tests in different stages of kidney transplantation (flow KT) would have significant importance.…”

Section: Introductionmentioning

confidence: 99%

Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines

Kang

Choi

Park

et al. 2018

Korean J Transplant

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Detection of significant alloimmune response, which affects graft function and survival by effective immune monitoring, is critical for treatment decision making. However, there is no consensus regarding immune monitoring (IM) for kidney transplantation (flow KT) in Korea. The IM protocol may be affected by the level of immunological risk, the methods of desensitization and the availabilities of resources such as laboratory support and cost of tests. Questionnaire surveys designed to identify the current practi- Until now, the immunological monitoring of alloimmune responses are focused on the detection of rejection events in practice than detection of adverse immune activity which might be preceded clinically or pathologically evident rejection signs. It might be rather because there were no reliable and well validated laboratory methods to be applicable.However, luminex bead technologies used for the detection of antibodies in antigen, allele or epitope levels for HLA(7-9) and non-HLA systems(15), and molecular technologies to detect transcript signatures of diverse immunologic changes are broadening our choice of tests(16-18).And it is continuously reflected on diagnostic criteria such as Banff criteria (19,20). However, the diagnostic criteria does not specify the practical way of immune monitoring in real world, so, there is no standardized guidelines and is Immune monitoring protocolsAbout 28% (9/32) of clinicians from 6 institutes (6/25, 24%) are performing protocol biopsies at various time points and the number of biopsy depending on the level of immunological risks (Fig. 3). When higher the risk, more frequent biopsies are being performed within posttransplant 12 weeks (Fig. 4). Clinicians are applying different combinations of HLA antibody tests in different time points and also depending on the level of immunological risks. Antibody monitoring is being performed frequently at posttransplant 3∼4 weeks, 24 weeks and yearly (Fig. 5). Antibody screening test is used for low risk patients, however for high risk patients, HLA antibody phenotyping or SAB identification tests are used more frequently (Fig. 6). The suggested time points of HLA antibody monitoring test in patients waiting for kidney transplantation was questioned regardless of current protocols (Fig. 7). Twenty-four out of 26 (92%) respondents answered that the presence of HLA antibody needed to be checked at registration in KONOS regardless of immunological risk levels, and for living donor kidney transplant (LDKT) candidates, it is suggested to do within pre-transplant 4 weeks. Twelve (46%) respondents replied that the monitoring of HLA antibody is necessary if the patients had recent transfusion or pregnancy episodes.As on-demand test when the rejection is suspected clinically, 70% (22/32) of respondents answered proceeding to HLA antibody test but 15% (5/32) answered to do HLA antibody test when the pathologic finding of AMR in biopsy identified (Fig. 8).2. sponses needs to be cautious because it may be rather because not all the instit...

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“…Several authors recently reported that a high PRA level, especially positive donor-specific antibody (DSA), was associated with not only AMR but also ACR. 23,24) Loupy, et al demonstrated that very late rejection at several years after HTx diagnosed as ≥ 2R ISHLT rejection was associated with complement-cascade activation and microvascular injury along with positive DSA, suggesting accompanied antibody-mediated process. 25) C4d deposition observed in all 5 LR (+) recipients at the time of LR was compatible with the finding of Loupy and coworkers that LR might have a component of the antibody-mediated process in addition to cellular rejection.…”

Section: Discussionmentioning

confidence: 99%

Late Rejection Occurred in Recipients Who Experienced Acute Cellular Rejection Within the First Year After Heart Transplantation

et al. 2015

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SummarySerial endomyocardial biopsies (EMBs) are scheduled even several years after heart transplantation (HTx) to monitor for late rejection (LR). However, repeated EMBs are associated with an increased risk for fatal complications and decrease the quality of life of the recipient. We retrospectively analyzed clinical data from 42 adult recipients who had received HTx and were followed > 1 year at the University of Tokyo Hospital. Five recipients experienced LR at 1130 ± 157 days after HTx, and all 5 had experienced acute cellular rejection (ACR) with ISHLT grade ≥ 2R within the first year, which was treated with methylprednisolone pulse therapy (sensitivity, 1.000; specificity, 0.7027). Logistic regression analyses demonstrated that positive panel reactive antibody (PRA) was the only significant predictor for LR among all parameters at 1 year after HTx (P = 0.020, odds ratio 24.00). Among the 5 recipients with LR, LR occurred earlier in the two PRA positive recipients than in those with a negative PRA (981 ± 12 versus 1230 ± 110 days, P = 0.042). Among the perioperative parameters, gender mismatch [n = 13 (31%)] was the only significant predictor for ACR within the first year in logistic regression analyses (P = 0.042, odds ratio 4.200). In conclusion, the current schedule of serial EMBs should perhaps be reconsidered for recipients without any history of ACR within the first year due to their lower risk of LR. (Int Heart J 2015; 56: 174-179)

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Increased Negative Impact of Donor HLA-Specific Together With Non-HLA–Specific Antibodies on Graft Outcome

Abstract: These results show the increased negative impact of dnDSA and AT1R-ab on freedom from AMR and/or CMR and an increased hazard ratio when both parameters are considered. Both HLA- and non-HLA-specific antibodies seem to impact graft outcome in heart transplantation.

Cited by 109 publications

References 47 publications

Optimizing transplantation of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens

Optimizing transplantation of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens

Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines

Late Rejection Occurred in Recipients Who Experienced Acute Cellular Rejection Within the First Year After Heart Transplantation

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