Screening strategy for de novo donor‐specific HLA antibodies beyond the first year after kidney transplantation: Personalized or “one size fits all”?

2020 ◽  
Author(s):  
Hasret Cun ◽  
Gideon Hönger ◽  
Marc Kleiser ◽  
Patrizia Amico ◽  
Caroline Wehmeier ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Screening Strategy ◽  
First Year ◽  
Hla Antibodies

scholarly journals The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Cristina Ribeiro de Castro ◽  
Erick A. Barbosa ◽  
Renata P. Souza ◽  
Fabiana Agena ◽  
Patrícia S. de Souza ◽  
...  
Keyword(s):  
Acute Rejection ◽  
De Novo ◽  
First Year ◽  
Sharp Drop ◽  
Hla Antibodies ◽  
Single Antigen ◽  
The Impact ◽  
Kinetics Of ◽  
Time Point ◽  
Rejection Rates

The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed “de novo” Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, p<0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.

De novo anti-HLA antibodies have the highest incidence in the first year after transplantation

2003 ◽  
Vol 64 (10) ◽  
pp. S31 ◽  
Author(s):  
Alin Girnita ◽  
Rene Duquesnoy ◽  
Anthony Demetris ◽  
Carol Bentlejewski ◽  
David Guaspari ◽  
...  
Keyword(s):  
De Novo ◽  
First Year ◽  
Hla Antibodies

Tac-MMF Versus CsA-MMF/CsA-AZA–Based Regimens in Development of De Novo Complement-Binding Anti-HLA Antibodies After Kidney Transplantation

2017 ◽  
Vol 49 (3) ◽  
pp. 454-459 ◽  
Author(s):  
T. Sahutoglu ◽  
S.U. Akgul ◽  
Y. Caliskan ◽  
H. Yazici ◽  
E. Demir ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Hla Antibodies

Post-transplant de novo non donor-specific HLA antibodies are not associated with poor graft outcome in non-sensitized pediatric recipients of kidney transplantation

2021 ◽  
Vol 65 ◽  
pp. 101375
Author(s):  
Michela Cioni ◽  
Patrizia Comoli ◽  
Augusto Tagliamacco ◽  
Annalisa Innocente ◽  
Sabrina Basso ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Hla Antibodies ◽  
Post Transplant ◽  
Graft Outcome ◽  
Pediatric Recipients

scholarly journals Characteristics and Clinical Significance of De Novo Donor-Specific Anti-HLA Antibodies after Kidney Transplantation

2018 ◽  
Vol 33 (34) ◽  
Author(s):  
Hee-Yeon Jung ◽  
Su-Hee Kim ◽  
Min-Young Seo ◽  
Sun-Young Cho ◽  
Youngae Yang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Clinical Significance ◽  
De Novo ◽  
Hla Antibodies

scholarly journals Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study

2020 ◽  
Vol 31 (9) ◽  
pp. 2193-2204 ◽  
Author(s):  
Aleksandar Senev ◽  
Maarten Coemans ◽  
Evelyne Lerut ◽  
Vicky Van Sandt ◽  
Johan Kerkhofs ◽  
...  
Keyword(s):  
Cohort Study ◽  
Kidney Transplantation ◽  
Graft Failure ◽  
De Novo ◽  
Multivariable Analysis ◽  
Hla Antibodies ◽  
Transplant Outcomes ◽  
Antibody Mediated Rejection ◽  
Kidney Recipients ◽  
Hla Dq

BackgroundIn kidney transplantation, evaluating mismatches of HLA eplets—small patches of surface-exposed amino acids of the HLA molecule—instead of antigen mismatches might offer a better approach to assessing donor-recipient HLA incompatibility and improve risk assessment and prediction of transplant outcomes.MethodsTo evaluate the effect of number of eplet mismatches (mismatch load) on de novo formation of donor-specific HLA antibodies (DSAs) and transplant outcomes, we conducted a cohort study that included consecutive adult kidney recipients transplanted at a single center from March 2004 to February 2013. We performed retrospective high-resolution genotyping of HLA loci of 926 transplant pairs and used the HLAMatchmaker computer algorithm to count HLA eplet mismatches.ResultsDe novo DSAs occurred in 43 (4.6%) patients. Multivariable analysis showed a significant independent association between antibody-verified eplet mismatch load and de novo DSA occurrence and graft failure, mainly explained by DQ antibody-verified eplet effects. The association with DQ antibody-verified eplet mismatches was linear, without a safe threshold at which de novo DSA did not occur. Odds for T cell– or antibody-mediated rejection increased by 5% and 12%, respectively, per antibody-verified DQ eplet mismatch.ConclusionsEplet mismatches in HLA-DQ confer substantial risk for de novo DSA formation, graft rejection, and graft failure after kidney transplantation. Mismatches in other loci seem to have less effect. The results suggest that antibody-verified HLA-DQ eplet mismatch load could be used to guide personalized post-transplant immunosuppression. Adoption of molecular matching for DQA1 and DQB1 alleles could also help to minimize de novo DSA formation and potentially improve transplant outcomes.

scholarly journals Monitoring Tacrolimus Trough Concentrations During the First Year After Kidney Transplantation: A National Retrospective Cohort Study

2020 ◽  
Vol 11 ◽  
Author(s):  
Sarah S. Alghanem ◽  
Moetaza M. Soliman ◽  
Ali A. Alibrahim ◽  
Osama Gheith ◽  
Ahmed S. Kenawy ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Side Effects ◽  
Trough Concentration ◽  
De Novo ◽  
Target Range ◽  
First Year ◽  
Trough Concentrations ◽  
Multifaceted Interventions ◽  
Hospital Protocol

Background: There is a lack of data in the literature on the evaluation of tacrolimus (TAC) dosage regimen and monitoring after kidney transplantation (KT) in Kuwait. The aim of the present study was to evaluate TAC dosing in relation to the hospital protocol, the achievement of target TAC trough concentration (C0), the prevalence of TAC side effects (SEs), namely, posttransplant diabetes mellitus (PTDM), denovo hypertension (HTN), and dyslipidemia, and factors associated with the occurrence of these SEs among KT recipients.Methods: A retrospective study was conducted among 298 KT recipients receiving TAC during the first year of PT. Descriptive and multivariate logistic regression analyses were used.Results: The initial TAC dosing as per the local hospital protocol was prescribed for 28.2% of patients. The proportion of patients who had C0 levels within the target range increased from 31.5 to 60.3% during week 1 through week 52. Among patients who did not have HTN, DM, or dyslipidemia before using TAC, 78.6, 35.2, and 51.9% of them were prescribed antihypertensive, antidiabetic, and antilipidemic medications during the follow-up period. Age of ≥40 years was significantly associated with the development of de novo HTN, dyslipidemia, and PTDM (p &lt; 0.05). High TAC trough concentration/daily dose (C0/D) ratio was significantly associated with the development of PTDM (p &lt; 0.05).Conclusion: Less than two-fifths of patients achieved target TAC C0 levels during the first month of PT. Side effects were more common in older patients. These findings warrant efforts to implement targeted multifaceted interventions to improve TAC prescribing and monitoring after KT.

scholarly journals Clinical Significance of Shared T Cell Epitope Analysis in Early De Novo Donor-Specific Anti-HLA Antibody Production After Kidney Transplantation and Comparison With Shared B cell Epitope Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Toshihide Tomosugi ◽  
Kenta Iwasaki ◽  
Shintaro Sakamoto ◽  
Matthias Niemann ◽  
Eric Spierings ◽  
...  
Keyword(s):  
T Cells ◽  
Kidney Transplantation ◽  
T Cell ◽  
De Novo ◽  
Memory T Cells ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
Hla Antibodies ◽  
Epitope Analysis ◽  
Hla Antibody

In pre-sensitizing events, immunological memory is mainly createdviaindirect allorecognition where CD4+T cells recognize foreign peptides in the context of self-HLA class II (pHLA) presented on antigen-presenting cells. This recognition makes it possible for naive CD4+T-helper cells to differentiate into memory cells, resulting in the creation of further antibody memory. These responses contribute to effective secretion of donor-specific anti-HLA antibodies (DSA) after second encounters with the same peptide. Preformed donor-reactive CD4+memory T cells may induce early immune responses after transplantation; however, the tools to evaluate them are limited. This study evaluated shared T cell epitopes (TEs) between the pre-sensitizing and donor HLA using anin silicoassay, an alternative to estimate donor-reactive CD4+memory T cells before transplantation. In 578 living donor kidney transplants without preformed DSA, 69 patients had anti-HLA antibodies before transplantation. Of them, 40 had shared TEs and were estimated to have donor-reactive CD4+memory T cells.De novoDSA formation in the early phase was significantly higher in the shared TE-positive group than in the anti-HLA antibody- and shared TE-negative groups (p=0.001 and p=0.02, respectively). In conclusion, evaluation of shared TEs for estimating preformed donor-reactive CD4+memory T cells may help predict the risk of earlyde novoDSA formation after kidney transplantation.

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