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. 2023 Sep 20;9(10):e1534.
doi: 10.1097/TXD.0000000000001534. eCollection 2023 Oct.

Recurrent Mild Acute Rejections and Donor-specific Antibodies as Risk Factors for Cardiac Allograft Vasculopathy in a National Pediatric Heart Transplant Cohort

Anu K Kaskinen  1 , Juuso Tainio  1 , Jaana I Pihkala  2 , Juha P Peräsaari  3 , Jouni Lauronen  3 , Alireza Raissadati  4 , Jussi M Merenmies  1 , Hannu J Jalanko  1 , Timo Jahnukainen  1
Affiliations

Recurrent Mild Acute Rejections and Donor-specific Antibodies as Risk Factors for Cardiac Allograft Vasculopathy in a National Pediatric Heart Transplant Cohort

Anu K Kaskinen et al. Transplant Direct. .

Abstract

Background: Immune-mediated factors such as acute cellular rejections and donor-specific antibodies (DSAs) are risk factors for cardiac allograft vasculopathy (CAV). We studied a national cohort with a unified setting and thorough protocol endomyocardial biopsy (EMB) data for an association between cellular rejections, especially when mild and recurrent, and DSAs with CAV in pediatric heart transplant (HTx) patients.

Methods: This is a retrospective, national cohort study of 94 pediatric HTxs performed between 1991 and 2019 and followed until December 31, 2020. Diagnosis of CAV was based on reevaluation of angiographies. Protocol and indication EMB findings with other patient data were collected from medical records. Associations between nonimmune and immune-mediated factors and CAV were analyzed with univariable and multivariable Cox regression analyses.

Results: Angiographies performed on 76 patients revealed CAV in 23 patients (30%). Altogether 1138 EMBs (92% protocol biopsies) were performed on 78 patients (83%). During the first posttransplant year, grade 1 rejection (G1R) appeared in 45 patients (58%), and recurrent (≥2) G1R findings in 14 patients (18%). Pretransplant DSAs occurred in 13 patients (17%) and posttransplant DSAs in 37 patients (39%). In univariable analysis, pretransplant DSAs, appearance and recurrence of G1R findings, and total rejection score during the first posttransplant year, as well as recurrent G1R during follow-up, were all associated with CAV. In multivariable analysis, pretransplant DSAs and recurrent G1R during the first posttransplant year were found to be associated with CAV.

Conclusions: Our results indicate that pretransplant DSA and recurrent G1R findings, especially during the first posttransplant year, are associated with CAV after pediatric HTx.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
Kaplan-Meier estimated CAV-free survival (A) and log-rank comparison of Kaplan-Meier estimated graft survival (B) between patients who developed CAV and those who did not. CAV, cardiac allograft vasculopathy; HTx, heart transplant.
FIGURE 2.
FIGURE 2.
Log-rank comparison of Kaplan-Meier estimated CAV-free survival in patients with and without pretransplant DSA (A), and in patients with and without recurrent G1Rs during the first posttransplant year (B). CAV, cardiac allograft vasculopathy; DSA, donor-specific antibody; G1R, grade 1 rejection; HTx, heart transplant.
See this image and copyright information in PMC

References

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