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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Alloimmunity and Transplantation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1659939

Angiotensin II Type 1 Receptor Antibodies as a Contributor to Microvascular Inflammation in Kidney Transplant Recipients: Insights from Statistical and Artificial Intelligence Based Approaches

Provisionally accepted
Jakub  MizeraJakub Mizera1,2*Piotr  DonizyPiotr Donizy1,2Agnieszka  HalonAgnieszka Halon1,2Dariusz  JanczakDariusz Janczak1,2Marta  KepinskaMarta Kepinska2Maciej  PondelMaciej Pondel3Miroslaw  BanasikMiroslaw Banasik1,2
  • 1Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu, Wrocław, Poland
  • 2Uniwersytet Medyczny im Piastow Slaskich we Wroclawiu, Wrocław, Poland
  • 3Uniwersytet Ekonomiczny we Wroclawiu, Wrocław, Poland

The final, formatted version of the article will be published soon.

Introduction: In recent years, advancements in the classification of renal allograft pathology have led to a notable increase in the diagnosis of antibody-mediated rejection (ABMR). Particular attention has been given to microvascular inflammation (MVI), a subcategory of ABMR that was reappraised in the Banff 2022 classification. Recognizing a significant discrepancy between the number of patients testing positive for donor-specific anti-HLA antibodies (DSAs) and those clinically diagnosed with ABMR, this study aims to explore the potential role of non-HLA antibodies, specifically, antibodies against the angiotensin II type 1 receptor (AT1R), in the development of MVI. Material and Methods: A retrospective analysis was performed on clinical and pathological data from 167 kidney transplant recipients. MVI was diagnosed histologically based on biopsy findings, specifically a glomerulitis score (g) > 0 and/or peritubular capillaritis (ptc) > 0. Based on these criteria, two patient cohorts were identified: 88 patients without MVI and 79 patients with MVI. Statistical analyses were conducted using appropriate methods, including chi-square tests, Student's t-tests, and Mann–Whitney U tests. Additionally, complementary analyses utilizing artificial intelligence techniques such as correlation analysis, logistic regression and association rule mining were applied to maximize insights from the dataset. Results: Patients with MVI demonstrated a statistically significantly higher prevalence of AT1R antibodies compared to those without MVI. The finding was confirmed by both traditional statistical methods and artificial intelligence analysis. Furthermore, the MVI-positive cohort exhibited a higher frequency of C4d positivity compared to patients without MVI. Conclusions: The presence of AT1R antibodies may be associated with the development of microvascular inflammation, potentially contributing to allograft injury in a subset of cases of kidney transplant recipients. High AT1R abs titers (>12 U/ml) were particularly important, while lower levels did not show the meaningful association. These findings underscore the importance of broadening immunologic surveillance beyond conventional anti-HLA antibody screening.

Keywords: Kidney Transplantation, artificial intelligence, Angiotensin II type 1 receptor antibodies, Non-HLA, microvascular inflammation

Received: 04 Jul 2025; Accepted: 02 Oct 2025.

Copyright: © 2025 Mizera, Donizy, Halon, Janczak, Kepinska, Pondel and Banasik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jakub Mizera, jakub.mizera@student.umw.edu.pl

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