Utility of routine immunofluorescence staining for C4d in cardiac transplant recipients
Sachin Gupta1, Joshua D Mitchell, Bhavna Lavingia
1Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9047, USA.
Insights
Routine C4d immunofluorescence staining in endomyocardial biopsies (EMB) can help diagnose antibody-mediated rejection in heart transplant recipients. Positive C4d staining correlates with acute cellular rejection and reduced graft function.
Area of Science:
- Cardiology
- Transplantation Immunology
- Pathology
Background:
- C4d immunofluorescence staining of endomyocardial biopsies (EMBs) aids in diagnosing antibody-mediated rejection.
- Limited data exist on the routine clinical utility of C4d staining in cardiac transplantation.
Purpose of the Study:
- To evaluate the clinical utility of routine C4d immunofluorescence staining in endomyocardial biopsy (EMB) specimens.
- To determine the association between C4d staining results and rejection patterns in adult cardiac transplant recipients.
Main Methods:
- Retrospective review of adult cardiac transplant recipients with at least two EMBs and C4d staining since 2006.
- Analysis of C4d staining results alongside routine hematoxylin and eosin staining, donor-specific antibodies (DSA), and clinical outcomes.
Main Results:
- 14 out of 67 patients had C4d-positive (C4d+) EMBs.
- C4d+ specimens were significantly associated with acute cellular rejection (ACR) (57% vs 11%, p < 0.001).
- Positive C4d staining correlated with positive retrospective crossmatch, presence of DSA post-transplant, and depressed graft function (p < 0.01).
Conclusions:
- Positive C4d staining on EMBs is linked to ACR, impaired allograft function, positive crossmatch, and DSA presence.
- These findings support C4d deposition as a marker for antibody-mediated rejection.
- Routine C4d evaluation is clinically feasible and can reveal diverse rejection patterns.
Background:
Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care.
Methods:
This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent > or = 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection.
Results:
Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each).
Conclusions:
Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.
