Angiotensin II type-1 receptor antibody (AT1Rab) associated humoral rejection and the effect of peri operative plasma exchange and candesartan

Carroll, Robert; Riceman, Michael; Hope, Christopher; Zeng, Anna; Deayton, Sue; Bennett, Greg; Coates, P. Toby

doi:10.1016/j.humimm.2016.08.009

Cited by 33 publications

(22 citation statements)

References 10 publications

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“…reported significant improvement in hypertension and aldosterone levels in two PA patients treated with losartan. A recent retrospective study on kidney transplant recipients reported that perioperative candesartan might alter the risk of rejection in patients with increased AT1RAb titer, reducing the AT1R‐mediated inflammatory response . All these findings suggest a potential therapeutic role of AT1R blockers and further studies should investigate in those patients with AT1RAb positivity the effects of AT1R blocker therapy not only on the blood pressure but also on the aldosterone levels.…”

Section: Discussionmentioning

confidence: 96%

Evaluation of angiotensin II type‐1 receptor antibodies in primary aldosteronism and further considerations about their possible pathogenetic role

Sabbadin

Ceccato

Ragazzi

et al. 2018

J of Clinical Hypertension

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Angiotensin II type-1 receptor autoantibodies (AT1RAb) have been involved in the genesis of primary aldosteronism (PA), both in aldosterone-producing adenoma (APA) and in idiopathic hyperaldosteronism (IHA). In this study, we evaluated the titer of AT1RAb in 44 PA patients (15 with APA and 29 with IHA) compared with 18 normotensive healthy controls who were matched for gender and age. In 17 PA patients (6 APA and 11 IHA) the titer was evaluated under mineralocorticoid receptor (MR) antagonist treatment. We found that PA patients had a significantly higher titer of AT1RAb compared with controls (median values 33 [IQR 15.6] IU/mL vs 17.5 [IQR 10.8] IU/mL, respectively; P < 0.0001). No significant difference of the AT1RAb titer was reported among PA patients, subdivided according to the subtypes and the concomitant MR antagonist therapy. No significant correlation was detected between age, gender, BMI, blood pressure values, baseline aldosterone, ARR, and the AT1RAb titer of all patients enrolled. Our data confirm an increased titer of AT1RAb in both subtypes of PA, independently from the concomitant use of MR antagonists and clinical/biochemical characteristics of PA patients. The small sample of patients and the relatively short time of treatment could have influenced these results. Moreover, the ELISA assay fails to evaluate the bioactivity of AT1RAb. Further studies should evaluate if the subtype, the clinical/biochemical recovery of PA, or both, influence the pathogenetic role of AT1RAb. The possible autoimmune pathogenesis and reversal effect with AT1R blocker treatment in PA patients with AT1RAb positivity is intriguing and requires further study.

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Section: Discussionmentioning

confidence: 96%

Evaluation of angiotensin II type‐1 receptor antibodies in primary aldosteronism and further considerations about their possible pathogenetic role

Sabbadin

Ceccato

Ragazzi

et al. 2018

J of Clinical Hypertension

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“…Ig, plasmapheresis, and angiotensin receptor blockade. 7,60,61 However, the role of ETAR blockade in transplantation has not yet been explored. The successful use of ETAR blockers to treat complications associated with ETAR-Ab has been reported in scleroderma.…”

Section: Discussionmentioning

confidence: 99%

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation

Pearl

Chen

ElChaki

et al. 2020

Kidney International Reports

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Introduction: Autoantibody to angiotensin II type 1 receptor (AT1R-Ab) has been recognized as a non-human leukocyte antigen (HLA) antibody relevant in transplantation. Endothelin type A receptor antibody (ETAR-Ab) has been strongly associated with AT1R-Ab, but the data in kidney transplantation are scarce. Methods: We examined the relationship of ETAR-Ab and AT1R-Ab with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibody (DSA) in a cohort of pediatric renal transplant recipients. Sixty-five patients were longitudinally monitored for ETAR-Ab, AT1R-Ab, HLA DSA, interleukin (IL)-8, tumor necrosis factor-a, IL-1b, interferon-g, IL-17, IL-6, renal dysfunction, hypertension, rejection, and allograft loss during the first 2 years post-transplant. Results: Fifteen patients (23%) had AT1R-Ab alone, 1 (2%) had ETAR-Ab alone, 23 (35%) had both ETAR-Ab and AT1R-Ab, and 26 (40%) were negative for both antibodies at all timepoints. Having both ETAR-Ab and AT1R-Ab was associated with >30% decline in estimated glomerular filtration rate (P ¼ 0.024), arteritis (P ¼ 0.016), and elevated IL-8 levels (P ¼ 0.010), but not rejection, HLA DSA, or allograft loss. Having both antibodies resulted in greater increases in IL-8 compared with AT1R-Ab alone, even when controlled for additional clinical factors, including HLA DSA (P ¼ 0.012). Conclusion: Our study demonstrates that, in pediatric kidney transplantation, ETAR-Ab is highly associated with AT1R-Ab, but there are a subset of patients with AT1R-Ab alone. Having both antibodies is significantly associated with arteritis, elevated IL-8, and decline in renal function, and our results suggest possible interaction effects. Better understanding of this interaction may be informative in developing protocols for testing, treatment, and prevention of allograft injury.

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“…Theoretically they may reduce the risk of de-novo development of AT1R-AA and DSA after transplantation, if given prophylactically. The ARB, candesartan, has been successfully used in combination with antibody-reduction therapy to manage kidney patients before transplantation (29) and to treat rejection in recipients who are positive for AT1R-AA (1, 30). Data from this report and others regarding AT1R-AA may be sufficient to justify a clinical trial of ARB in liver transplantation.…”

Section: Accepted Articlementioning

confidence: 99%

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

McAlister

Leckie

et al. 2020

American Journal of Transplantation

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Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R-AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R-AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R-AA before transplantation were higher (p=0.019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R-AA>17U/ml before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R-AA (defined as >40U/ml) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan-Meier analysis, patients with strong positive AT1R-AA had significantly worse graft survival than those with Accepted Article This article is protected by copyright. All rights reserved. AT1R-AA<40U/ml (p=0.035). In multivariate Cox models that included confounders such as sex and age, either AT1R-AA>40U/ml [HR=1.999 (1.085-3.682), p=0.026] or increased concentrations of AT1R-AA [HR=1.003 (1.001-1.006) per incremental U/ml, p=0.019] were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R-AA in candidates for second liver transplantation and that their presence is associated with inferior long-term outcomes of the second graft.

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Angiotensin II type-1 receptor antibody (AT1Rab) associated humoral rejection and the effect of peri operative plasma exchange and candesartan

Cited by 33 publications

References 10 publications

Evaluation of angiotensin II type‐1 receptor antibodies in primary aldosteronism and further considerations about their possible pathogenetic role

Evaluation of angiotensin II type‐1 receptor antibodies in primary aldosteronism and further considerations about their possible pathogenetic role

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

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