Dynamics of anti‐human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome

Souza, Paulo Sérgio Lopes de; David‐Neto, Elias; Panajotopolous, Nicolas; Agena, Fabiana; Rodrigues, H.; Ronda, C; David, Débora Leite; Kalil, Jorge; Nahas, W. C.; Castro, Maria Cristina Ribeiro de

doi:10.1111/ctr.12451

Cited by 8 publications

(12 citation statements)

References 30 publications

(39 reference statements)

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“…Some studies have shown no differences in mean pretransplant MFIs among patients with and without ABMR, although patients with higher levels present higher ABMR [ 11 , 12 ]. This data confirmed our previous results obtained using an ELISA-PRA test for posttransplant monitoring [ 7 ].…”

Section: Discussionsupporting

confidence: 92%

“…DSA measure is a noninvasive procedure and may help in the early diagnosis of ABMR, resulting in a strong impact on graft survival [ 1 , 2 , 7 , 11 , 15 , 16 ]. In addition, we observed that monitoring DSA helped to follow patients treated for ABMR.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously studied the kinetics of anti-HLA Abs after kidney transplantation using ELISA-Panel Reactive Antibodies (ELISA-PRA) determination and showed that the increase in ELISA-PRA levels was associated with the occurrence of acute antibody-mediated rejection [ 7 ]. Also, in a retrospective analysis of anti-HLA Abs after KTx, we have observed that most of the patients with pre-Tx DSA, whose graft survived after 6 years of follow-up, had cleared/decreased their pre-Tx Abs after KTx [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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

Castro

Barbosa

Souza

et al. 2018

Journal of Transplantation

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Castro

Barbosa

Souza

et al. 2018

Journal of Transplantation

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“…One hundred and ninety‐nine recipients received antibody‐incompatible renal transplants between 2005 and 2015 at the four transplant centres, of whom 139 met the inclusion criteria and comprised the final study cohort. We analysed pretreatment (pretransplant sample before plasmapheresis and/or IVIG) and Day 14 samples [18,31‐33]. Pretreatment serum samples were available for 139 recipients, but post‐transplant Day 14 samples were only available for 111 recipients.…”

Section: Concise Materials and Methodsmentioning

confidence: 99%

C3d‐positive donor‐specific antibodies have a role in pretransplant risk stratification of cross‐match‐positive HLA‐incompatible renal transplantation: United Kingdom multicentre study

Babu

Khovanova

Shaw³

et al. 2020

Transpl Int

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Anti‐HLA‐antibody characteristics aid to risk‐stratify patients and improve long‐term renal graft outcomes. Complement activation by donor‐specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross‐match‐positive). We explored the role of C3d‐positive DSAs in sub‐stratification of cross‐match‐positive cases and relate to the graft outcomes. We investigated 139 cross‐match‐positive living‐donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post‐transplant. C3d‐positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post‐transplant. Median follow‐up of patients was 48 months (IQR 20.47–77.57). In the multivariable analysis, pretreatment C3d‐positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37–7.86). The relative risk of death‐censored five‐year graft failure was 2.83 (95% CI 1.56–5.13). Patients with both pretreatment and Day 14 C3d‐positive DSAs had the worst five‐year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d‐negative DSA patients with the relative risk of death‐censored five‐year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub‐stratify the risk of poor graft outcome in cross‐match‐positive living‐donor renal transplantation.

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“…(2) Apart from direct measurement of immune cell subsets, quantifying their products such as chemokines, cytokines or antibodies has become a valuable diagnostic opportunity [89,[100][101][102]. Analysis of donor (MHC)-specific antibodies (DSA) has been used for decades to guide donor-recipient-matching in the pretransplant phase [103,104] or to diagnose humoral rejection episodes, especially after kidney transplantation [105][106][107][108][109][110][111]. However, during the last 10 years it has become evident that detection of non-human leucocyte antigen (HLA) antibodies such as anti-MHC class I chain-related protein A (MICA), anti-angiotensin receptor or anti-endothelin receptor Box 1.…”

Section: Examples Of Already Described Biomarkers and Potential Assaysmentioning

confidence: 99%

Immune monitoring as prerequisite for transplantation tolerance trials

Sani

Sawitzki

2017

Clinical and Experimental Immunology

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SummaryEver since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of ISinduced side effects, which are contributing to the still unsatisfactory longterm graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients. These approaches are based on (i) IS withdrawal in spontaneous operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and (iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing these approaches show that tolerance induction does not work in all patients. Thus, there is a need for reliable biomarkers, which can be used for patient selection and post-therapeutic immune monitoring of safety, success and failure. In this review, we summarize recent achievements in the identification and validation of such immunological assays and biomarkers, focusing mainly on kidney and liver transplantation. From the published findings so far, it has become clear that indicative biomarkers may vary between different therapeutic approaches applied and organs transplanted. Also, patient numbers studied so far are very small. This is the main reason why nearly all described parameters lack validation and reproducibility testing in large clinical trials, and are therefore not yet suitable for clinical practice.

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Dynamics of anti‐human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome

Cited by 8 publications

References 30 publications

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

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

C3d‐positive donor‐specific antibodies have a role in pretransplant risk stratification of cross‐match‐positive HLA‐incompatible renal transplantation: United Kingdom multicentre study

Immune monitoring as prerequisite for transplantation tolerance trials

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