Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and Multivisceral Transplantation

Gerlach, Undine; Lachmann, Nils; Ranucci, Giuseppina; Sawitzki, Birgit; Schoenemann, Constanze; Pratschke, Johann; Dragun, Duska; Pascher, Andreas

doi:10.1097/tp.0000000000001439

Cited by 32 publications

(28 citation statements)

References 39 publications

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“…Since then, multiple studies have shown reduced kidney graft survival with AT1R-AA, but the effects on rejection and malignant hypertension are less certain (2)(3)(4)(5). Similar negative effects have been reported for heart, lung, and intestine transplants, especially when donor-specific antibodies (DSA) were also present (6)(7)(8).…”

Section: Introductionmentioning

confidence: 76%

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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Section: Introductionmentioning

confidence: 76%

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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“…[23][24][25][26] The pathophysiology of AT1R-Ab has been linked to increased endothelin-1 and activation of ETAR 27,28 and, importantly, clinical disease severity in both systemic sclerosis and preeclampsia has been correlated with the activation of both pathways. 25,26 The strong association of AT1R-Ab and ETAR-Ab has also been described in solid-organ transplantation [29][30][31][32] ; however, the data in kidney transplantation 19,20 are scarce and limited to adult studies.…”

mentioning

confidence: 96%

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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“…Formation of these antibodies may actually precede HLA antibodies (DSA) and thus trigger a more forceful immunologic response. Furthermore, patients with non-HLA antibodies also had a higher frequency of rejection than controls (80 vs 55%) [43]. These markers might be useful in clinical practice but needs to be investigated in larger studies priorly.…”

Section: Donor-specific Antibodiesmentioning

confidence: 98%

Graft assessment for acute rejection after intestinal transplantation: current status and future perspective

Varkey

2020

Scandinavian Journal of Gastroenterology

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Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and Multivisceral Transplantation

Cited by 32 publications

References 39 publications

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

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

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

Graft assessment for acute rejection after intestinal transplantation: current status and future perspective

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