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Observational Study
. 2018 Sep;18(9):2163-2174.
doi: 10.1111/ajt.14691. Epub 2018 Mar 24.

Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC-04 study

A I Dipchand  1 , S Webber  2 , K Mason  3 , B Feingold  4 , C Bentlejewski  5 , W T Mahle  6 , R Shaddy  7 , C Canter  8 , E D Blume  9 , J Lamour  10 , W Zuckerman  11 , H Diop  12 , Y Morrison  12 , B Armstrong  3 , D Ikle  3 , J Odim  12 , A Zeevi  5 ; CTOTC-04 Investigators
Affiliations
Observational Study

Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC-04 study

A I Dipchand et al. Am J Transplant. 2018 Sep.

Abstract

Data on the clinical importance of newly detected donor-specific anti-HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One-third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first-year ndDSAs is being assessed in an extended cohort of patients.

Keywords: clinical research/practice; heart transplantation/cardiology; monitoring: immune; patient survival; pediatrics; rejection: acute; rejection: antibody-mediated (ABMR); sensitization.

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Conflict of interest statement

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

Figure 1
Figure 1. Patient population grouped by pre-transplant (PreTx) antibody (Ab) status and subsequent development of newly detected DSA (ndDSA) categorized into Early and Late
The pre-transplant antibody negative and pre-transplant antibody positive without DSA groups together formed the pre-transplant non-DSA cohort, n=186 (gray boxes). *Numbers in [square brackets] reflect Luminex LABScreen® Mixed; results in bold font reflect Luminex LABScreen® Single Antigen from the secondary analysis. See Methods: Study Definition and Alloantibody Core Evaluation.
Figure 2
Figure 2
Time course of newly detected DSA (ndDSA). Time to first ndDSA detection (in days from transplant) on a by subject basis. Each subject (n=80) is only shown once at the first time of detection of a ndDSA.
Figure 3
Figure 3. Freedom from acute cellular rejection (Panel A), antibody mediated rejection (Panel B) and rejection with hemodynamic compromise (Panel C) in pre-transplant DSA negative patients (n=186) stratified by Early (blue), Late (red) and No (green) newly detected DSA post-transplant
Estimated using the Kaplan-Meier method and compared with the Wilcoxon test.
Figure 4
Figure 4. Time course of post-transplant newly detected DSA in relation to rejection events
Subjects without DSA pre-transplant (n=55). The timing of the first ndDSA is represented by a blue star with timing and type of rejection depicted by colored circles.
Figure 5
Figure 5. Patient survival stratified by Early (blue), Late (red), and no (green) newly detected DSA (ndDSA) post-transplant
Panel A: Entire cohort (n=237), Panel B: Pre-transplant DSA negative (n=186), Panel C: Pre-transplant DSA positive (n=51). Estimated using the Kaplan-Meier method and compared with the Wilcoxon test.
See this image and copyright information in PMC

Comment in

References

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