Pre-transplant Screening for Non-HLA Antibodies: Who should be Tested?

Philogene, Mary Carmelle; Zhou, Sheng; Lonze, Bonnie E.; Bagnasco, Serena M.; Alasfar, Sami; Montgomery, Robert A.; Kraus, Edward S.; Jackson, Annette M.; Leffell, Mary S.; Zachary, Andrea A.

doi:10.1016/j.humimm.2018.02.001

Cited by 35 publications

(36 citation statements)

References 44 publications

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“…Preformed AT1R-AA were reported to be positive in 17-25% of patients before kidney transplantation (3,(10)(11)(12) and were usually more prevalent in kidney retransplant patients (3,11). We have speculated previously that low prevalence makes it difficult to see the effects of DSA on liver transplantation and that candidates for re-transplantation may make a better test cohort because of higher prevalence of DSA (13).…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Previous studies have provided evidence for the association between non-HLA antibodies, such as angiotensin II type 1 receptor antibodies (anti-AT1Rs) and anti-endothelial cell antibodies (AECAs), and acute rejection (AR) and/or graft failure [3][4][5][6][7][8][9][10][11][12][13]. Indeed, the allograft endothelium is the first barrier between self and non-self in vascularized solid organ transplantations and an active target of the host immune response [14].…”

Section: Introductionmentioning

confidence: 99%

Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting

Huh

Lee

et al. 2020

Ann Lab Med

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Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. Results: Pre-transplant anti-AT1Rs (≥ 11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P = 0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P = 0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥ 11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P < 0.001; P = 0.028), although the risk of AR was not significant. Conclusions: Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.

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“…We report the case of a patient who was desensitized to remove high-strength non-HLA antibody and underwent a successful deceased donor kidney transplant. Non-HLA antibodies are increasingly being recognized as entities that can cause antibody-mediated rejection and lead to accelerated graft loss [14,17]. In this patient, CDC crossmatches with numerous prior deceased donor offers were repeatedly positive.…”

Section: Discussionmentioning

confidence: 83%

“…Testing. Testing for the AT1R antibody was performed using quantitative ELISA (One Lambda, Thermo Fisher, West Hills, CA) as described elsewhere [14]. Endothelial crossmatch assays for the detection of AECA were performed using surrogate blood according to protocols previously reported [19].…”

Section: Endothelial Cell Crossmatching and At1r Antibodymentioning

confidence: 99%

“…Antiendothelial cell antibody (AECA) and antibody directed against the angiotensin II type 1 receptor (AT1R) are among the best characterized non-HLA antibodies [10]. A mounting body of evidence points to the association of non-HLA anti-body with risk for rejection and overall poorer long-term outcomes posttransplant [5,6,8,[11][12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Successful A2 to B Deceased Donor Kidney Transplant after Desensitization for High-Strength Non-HLA Antibody Made Possible by Utilizing a Hepatitis C Positive Donor

Karpel

Ali

Lawson

et al. 2020

Case Reports in Transplantation

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Desensitization using plasma exchange can remove harmful antibodies prior to transplantation and mitigate risks for hyperacute and severe early acute antibody-mediated rejection. Traditionally, the use of plasma exchange requires a living donor so that the timing of treatments relative to transplant can be planned. Non-HLA antibody is increasingly recognized as capable of causing antibody-mediated renal allograft rejection and has been associated with decreased graft longevity. Our patient had highstrength non-HLA antibody deemed prohibitive to transplantation without desensitization, but no living donors. As the patient was eligible to receive an A2 ABO blood group organ and was willing to accept a hepatitis C positive donor kidney, this afforded a high probability of receiving an offer within a short enough time frame to attempt empiric desensitization in anticipation of a deceased donor transplant. Fifteen plasma exchange treatments were performed before the patient received an organ offer, and the patient was successfully transplanted. Hepatitis C infection was treated posttransplant. No episodes of rejection were observed. At one-year posttransplant, the patient maintains good graft function. In this case, willingness to consider nontraditional donor organs enabled us to mimic living donor desensitization using a deceased donor.

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Pre-transplant Screening for Non-HLA Antibodies: Who should be Tested?

Cited by 35 publications

References 44 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

Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting

Successful A2 to B Deceased Donor Kidney Transplant after Desensitization for High-Strength Non-HLA Antibody Made Possible by Utilizing a Hepatitis C Positive Donor

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