Non‐HLA AT1R antibodies are highly prevalent after pediatric intestinal transplantation

Chan, Alvin P.; Guerra, Marjorie-Anne R.; Rossetti, Maura; Hickey, Michelle J.; Venick, Robert S.; Marcus, Elizabeth A.; McDiarmid, Suzanne V.; Farmer, Douglas G.; Reed, Elaine F.; Wozniak, Laura J.

doi:10.1111/petr.13987

Cited by 5 publications

(6 citation statements)

References 31 publications

(86 reference statements)

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“…Most manuscripts assessing AT1R antibodies focus on kidney transplant recipients, 13,30,[33][34][35][36][37][38][39] with limited studies for other organs. [40][41][42][43][44][45] Generally, study cohorts included both patients with and without HLA-DSAs and were either underpowered or not designed to assess the effects of pretransplant non-HLA antibodies. 13,33,35,36 There have been several small (n ¼ 62-101) high-quality studies 12,[38][39][40]44,46 that performed comprehensive HLA evaluation (typing and antibody testing) to study the impact of pretransplant AT1R antibodies.…”

Section: At1r/etarmentioning

confidence: 99%

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

Tambur¹,

Bestard²,

Campbell³

et al. 2023

American Journal of Transplantation

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Section: At1r/etarmentioning

confidence: 99%

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

Tambur¹,

Bestard²,

Campbell³

et al. 2023

American Journal of Transplantation

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“…In a longitudinal study of 65 pediatric renal transplant recipients, AT1R‐Ab >17 U/ml was detected in 58% of the cohort at any time pre‐transplant to 2 years post‐transplant (17). In pediatric intestinal transplantation, AT1R‐Ab was detected in 68% of a transplant cohort compared to 29% of those with intestinal failure with higher median AT1R‐Ab level among transplant recipients (40.0 U/ml) compared to 7.0 U/ml with intestinal failure patients (43). The trigger for AT1R‐Ab development and reason for possible higher AT1R‐Ab levels in children remain unclear (25,44).…”

Section: Discussionmentioning

confidence: 99%

“…In pediatric intestinal transplantation, AT1R-Ab was detected in 68% of a transplant cohort compared to 29% of those with intestinal failure with higher median AT1R-Ab level among transplant recipients (40.0 U/ml) compared to 7.0 U/ml with intestinal failure patients (43). The trigger for AT1R-Ab development and reason for possible higher AT1R-Ab levels in children remain unclear (25,44).…”

Section: Ta B L E 2 Estimated Gfr Over Timementioning

confidence: 99%

“…The trigger for AT1R-Ab development and reason for possible higher AT1R-Ab levels in children remain unclear (25,44). Proposed mechanisms behind the development of AT1R-Ab include exposure of previously hidden antigens following tissue damage and ischemia reperfusion injury involved with organ transplantation (26,(43)(44)(45). Hesemann and colleagues found that in their cohort of 29 pediatric renal transplant recipients, there were no kidney-associated self-antigens (AT1R-Ab, fibronectin, collagen IV) pre-transplant compared with 50% of subjects that developed one or more of these antigens post-transplant, with a majority positive for AT1R-Ab (26).…”

Section: Ta B L E 2 Estimated Gfr Over Timementioning

confidence: 99%

See 1 more Smart Citation

Pre‐transplant angiotensin II receptor type I antibodies in pediatric renal transplant recipients: An observational cohort study

Pizzo

Mirocha

Choi

et al. 2022

Pediatric Transplantation

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Background The role of angiotensin II type 1 receptor antibodies (AT1R‐Ab) in pediatric renal transplantation is unclear. Here, we evaluated pre‐transplant AT1R‐Ab on transplant outcomes in the first 5 years. Secondary analysis compared pre‐transplant AT1R‐Ab levels by age. Methods Thirty‐six patients, 2–20 years old, were divided into two groups: pre‐transplant AT1R‐Ab− (<17 U/ml; n = 18) and pre‐transplant AT1R‐Ab+ (≥17 U/ml; n = 18). eGFR was determined at 6‐month, 1‐, 2‐, and 4‐year post‐transplant. Allograft biopsies were performed in the setting of strong HLA‐DSA (MFI > 10 000), AT1R‐Ab ≥17 U/ml, and/or elevated creatinine. Results Mean age in pre‐transplant AT1R‐Ab− was 13.3 years vs. 11.0 in pre‐transplant AT1R‐Ab+ (p = 0.16). At 6 months, mean eGFR was 111.3 ml/min/1.73 m2 in pre‐transplant AT1R‐Ab− vs. 100.2 in pre‐transplant AT1R‐Ab + at 1 year, 103.6 ml/min/1.73 m2 vs. 100.5; at 2 years, 98.9 ml/min/1.73 m2 vs. and 93.7; at 4 years, 72.6 ml/min/1.73 m2 vs. 80.9. 11/36 patients had acute rejection (6 in pre‐transplant AT1R‐Ab−, 5 in pre‐transplant AT1R‐Ab + ). There was no difference in rejection rates. All 6 subjects with de novo HLA‐DSA and AT1R‐Ab ≥17 U/ml at the time of biopsy experienced rejection. Mean age in those with the AT1R‐Ab ≥40 U/ml was 10.0 years vs. 13.2 in those <40 U/ml (p = 0.07). Conclusion In our small cohort, pre‐transplant AT1R‐Ab ≥17 U/ml was not associated with reduced graft function or rejection. The pathogenicity of pre‐transplant AT1R‐Ab in pediatric kidney transplantation requires further investigation.

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“…Although several non-HLA antibody specificities have been identified using laboratory-developed assays, large cohort studies into the role of non-HLA antibodies have used commercially available assays (8,21,22). The most reported non-HLA antibodies are directed against angiotensin II type 1 receptor (AT 1 R), MHC class I chain-related antigen A (MICA), tubulin, vimentin, endothelin receptors, collagens, and antiendothelial cell antibodies (AECAs), using either commercially available or laboratory-developed assays (6,7,23). However, despite a large number of published assays, screening for the presence of non-HLA antibodies has still not entered routine clinical practice in transplant medicine.…”

Section: Introductionmentioning

confidence: 99%

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

et al. 2022

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To date, human leukocyte antigens (HLA) have been the major focus in the approach to acute and chronic antibody-mediated rejection (AMBR) in solid-organ transplantation. However, evidence from the clinic and published studies has shown that non-HLA antibodies, particularly anti-endothelial cell antibodies (AECAs), are found either in the context of AMBR or synergistically in the presence of donor-specific anti-HLA antibodies (DSA). Numerous studies have explored the influence of AECAs on clinical outcomes, yet the determination of the exact clinical relevance of non-HLA antibodies in organ transplantation is not fully established. This is due to highly heterogeneous study designs including differences in testing methods and outcome measures. Efforts to develop reliable and sensitive diagnostic non-HLA antibody tests are continuously made. This is essential considering the technical difficulties of non-HLA antibody assays and the large variation in reported incidences of antibodies. In addition, it is important to take donor specificity into account in order to draw clinically relevant conclusions from non-HLA antibody assays. Here, we provide an overview of non-HLA solid-phase and cell-based crossmatch assays for use in solid-organ transplantation that are currently available, either in a research setting or commercially.

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Non‐HLA AT1R antibodies are highly prevalent after pediatric intestinal transplantation

Cited by 5 publications

References 31 publications

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

Pre‐transplant angiotensin II receptor type I antibodies in pediatric renal transplant recipients: An observational cohort study

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

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