The Presence of Anti-Angiotensin II Type-1 Receptor Antibodies Adversely Affect Kidney Graft Outcomes

Zhang, Jian; Wang, Mingxu; Liang, Jun; Zhang, Ming; Liu, Xiaohong; Ma, Le

doi:10.3390/ijerph14050500

Cited by 6 publications

(5 citation statements)

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“…We report here a strong and independent association between pre-transplant AT 1 R-Ab and ABMR h DSA pos development. AT 1 R can be found in several cell types such as vascular endothelial cells and binds to angiotensin II (39,47). First report linking AT 1 R-Ab and kidney allograft rejection suggested a potential relationship between AT 1 R agonistic antibodies and vascular injury (19,39).…”

Section: Discussionmentioning

confidence: 99%

Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection

et al. 2021

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BackgroundCorrelation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.MethodsWe retrospectively assessed patients with transplant biopsies scored following Banff’15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA.ResultsOne-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31–10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78–16.76], p = 0.003) were independent predictors of ABMRhDSApos.ConclusionsIn conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.

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Section: Discussionmentioning

confidence: 99%

Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection

et al. 2021

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“…Since the original paper describing AT1R-Ab in patients with acute AMR and hypertension, 8 multiple studies9, 16, 17, 33, 34, 35, 36, 37, 38, 39, 40 have indicated an association between AT1R-Ab with vascular inflammation and poor clinical outcomes. Studies with longitudinal measurements of AT1R-Ab9, 16, 36 remain limited.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies

Pearl

Grotts

Rossetti

et al. 2019

Kidney International Reports

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Introduction Angiotensin II type 1 receptor antibody (AT1R-Ab), is a non–human leukocyte antigen (HLA) antibody implicated in poor renal allograft outcomes, although its actions may be mediated through a different pathway than HLA donor-specific antibodies (DSAs). Our aim was to examine serum cytokine profiles associated with AT1R-Ab and distinguish them from those associated with HLA DSA in serially collected blood samples from a cohort of pediatric renal transplant recipients. Methods Blood samples from 65 pediatric renal transplant recipients drawn during the first 3 months posttransplant, at 6, 12, and 24 months posttransplant, and during suspected episodes of kidney transplant rejection were tested for AT1R-Ab, HLA DSA, and a panel of 6 cytokines (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-8, IL-1β, IL-6, and IL-17). Associations between antibodies and cytokines were evaluated. Results AT1R-Ab, but not HLA DSA, was associated with elevations in TNF-α, IFN-γ, IL-8, IL-1β, IL-6, and IL-17. This relationship remained significant even after controlling for relevant clinical factors and was consistent across all time points. In contrast to HLA DSA, AT1R-Ab was associated with elevations in vascular inflammatory cytokines in the first 2 years posttransplant. Conclusions This profile of vascular cytokines may be informative for clinical monitoring and designing future studies to delineate the distinct pathophysiology of AT1R-Ab–mediated allograft injury in kidney transplantation.

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“…A recent meta‐analysis found a significant effect of AT1R‐Abs on the allograft outcome, without considering neither the threshold of AT1R‐Ab positivity nor the HLA‐Ab detection technology. A new meta‐analysis considering our new study could be interesting .…”

Section: Discussionmentioning

confidence: 99%

“…Dragun et al [8,13] have shown for the first time their involvement in patients presenting acute rejection episodes (ARE) with severe hypertensive crisis. Since this first observation, the correlation of anti-AT1R antibodies and acute rejection and/or graft failure has become more debated in kidney transplantation sometimes due to a lack of power of studies [15][16][17][18][19][20][21][22][23][24]. In 2013, we showed on a large monocentric cohort (n = 599) of French kidney recipients that patients who displayed a pretransplant AT1R-Ab level above 10 U/ml had higher risk of acute rejection episodes within the first month following transplantation and graft failure beyond 3 years post-transplantation [25,26].…”

Section: Introductionmentioning

confidence: 99%

Is pre-transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti-HLA Luminex era? A retrospective study

Deltombe

Gillaizeau

et al. 2017

Transpl Int

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We aimed to assess the correlation of anti-angiotensin II type 1 receptor antibodies (anti-AT1R-Abs) before transplantation on a multicentric cohort of kidney transplant recipients (2008-2012), under tacrolimus and mycophenolate mofetil (MMF), screened by Luminex technology for anti-HLA immunization. Anti-AT1R antibody levels were measured by ELISA in pretransplantation sera of 940 kidney recipients from three French centers of the DIVAT cohort. Multivariable Cox models estimated the association between pretransplant anti-angiotensin II type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R-Abs higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative probability of clinically relevant (cr)-ARE was 22.5% at 1 year post-transplantation [95% CI (19.9-25.4%)]. The cumulative probability of graft failure and patient death were 10.6% [95% CI (8.4-13.3%)] and 5.7% [95% CI (4.0-8.1%)] at 3 years post-transplantation, respectively. Multivariate Cox models indicated that pretransplant anti-AT1R antibody levels higher than 10 U/ml were not significantly independently associated with higher risks of acute rejection episodes [HR = 1.04, 95% CI (0.80-1.35)] nor with risk of graft failure [HR = 0.86, 95% CI (0.56-1.33)]. Our study did not confirm an association between pretransplant anti-AT1R antibody levels and kidney transplant outcomes.

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The Presence of Anti-Angiotensin II Type-1 Receptor Antibodies Adversely Affect Kidney Graft Outcomes

Cited by 6 publications

References 38 publications

Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection

Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection

Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies

Is pre-transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti-HLA Luminex era? A retrospective study

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