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Updated: Jun 28, 2026
Murine Heterotopic Heart Transplant Technique
Published on: July 8, 2014
Complement fragment C4d and C3d deposition in pediatric heart recipients with a positive crossmatch
Dudley B Holt1, Helen Liapis, Thalchallour Mohanakumar
1Departments of Pediatrics, Pathology and Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1014, USA.
Insights
Pediatric heart transplant patients with positive crossmatches universally show C3d deposition. C4d deposition and macrophages appear in some, but not all, rejection cases, requiring further study.
Area of Science:
- Transplant immunology
- Pediatric cardiology
- Histopathology
Background:
- Pediatric heart transplant recipients with positive crossmatches face high rejection risk.
- Antibody-mediated rejection (AMR) markers like C3d, C4d, and macrophages are under investigation.
- Correlating deposition patterns with clinical rejection is crucial.
Purpose of the Study:
- To correlate C3d and C4d myocardial capillary deposition patterns with clinical rejection evidence.
- To assess pericapillary macrophage infiltration as a marker for rejection in pediatric heart transplant recipients.
- To investigate the significance of complement deposition and macrophage infiltration in high-risk pediatric heart transplants.
Main Methods:
- Studied 15 pre-sensitized pediatric patients with 21 rejection episodes.
- Analyzed 74 endomyocardial biopsies using immunoperoxidase staining for C3d, C4d, and CD68.
- Defined rejection by ISHLT biopsy Grade ≥2R and/or abnormal left ventricular function.
Main Results:
- C3d deposition was universally present (100%) in all biopsies.
- C4d deposition occurred in 8% of biopsies, associated with ISHLT Grade ≥2R cellular infiltration.
- Pericapillary macrophage infiltration (CD68+) was found in 46% of biopsies, linked to ISHLT Grade ≥2R in 29%.
Conclusions:
- C3d deposition is a universal finding in pediatric heart transplants with positive crossmatches.
- C4d deposition and macrophage infiltration are present in some, but not all, rejection episodes.
- Further research is needed to clarify the role of complement fragments and macrophages in endomyocardial biopsies.
Background:
Pediatric heart transplant recipients with a positive complement-dependent cytotoxic (CDC) donor-recipient crossmatch are at high risk for rejection. We sought to correlate the pattern of C3d and C4d myocardial capillary deposition and pericapillary macrophage infiltration, possible markers of antibody-mediated rejection, to clinical evidence of rejection in these patients.
Methods:
Were studied 15 pre-sensitized pediatric patients who had 21 rejection episodes, as defined by International Society for Heart and Lung Transplantation (ISHLT) biopsy Grade >or=2R and/or the development of abnormal left ventricular (LV) function at >1 week after transplant. Archived paraffin-embedded endomyocardial biopsies (n = 74) from these patients were subjected to immunoperoxidase staining for C3d, C4d and CD68 in duplicate. Positive and negative controls were included for each assay.
Results:
C3d deposition was present in 74 of 74 (100%) specimens. C4d deposition was present in 6 of 74 (8%) biopsies from 4 patients. Biopsies with C4d deposition had ISHLT Grade >or=2R cellular infiltration in 5 of 6 specimens. Pericapillary macrophage infiltration, defined as positive staining for CD68, was found in 34 of 74 (46%) biopsies, and was associated with ISHLT Grade >or=2R in 10 of 34 (29%).
Conclusions:
C3d deposition was universally present after heart transplantation with a CDC(+) donor/recipient crossmatch. C4d deposition and pericapillary macrophage infiltration were found with some, but not all, episodes of rejection. Further study is needed to understand the significance of the presence of complement fragments and pericapillary macrophage infiltration in these endomyocardial biopsies.
