Abstract 14113: Capillary Complement Deposition in Myocardium- An Unspecific Finding?
Objective: The nomenclature of antibody-mediated rejection (AMR) in cardiac allografts has been revised several times. Since the latest consensus paper of the International Society of Heart and Lung Transplantation, the diagnosis is solely based on histopathological findings. The recommended diagnostic antibody panel differs depending on the histopathological technique chosen. For formalin-fixed paraffin-embedded tissues (FFPE), endothelial cell swelling and interstitial capillary C4d depositions - a complement degradation product of the classical complement pathway - are defined as basic criteria.
We hypothesised that capillary C4d depositions, in small quantities, are an unspecific finding in the myocardium of patients with end-stage heart failure.
Material and Methods: We studied FFPE from LV myocardium from the site of mechanical circulatory support (MCS) implantation of 16 consecutive patients (4 female, 2-75 years old) with end stage heart failure (10 pts with dilatative cardiomyopathy (DCM), 4 pts with ischemic cardiomyopathy (ICM), one pt with valvular CM and one pt with congenital heart malformation). The sections were examined for chronic inflammation with a pan macrophage marker (CD68), a T-cell marker (CD3), for collagen depositions both with an immunohistochemical (collagen 3) and a histochemical marker (Sirius red). Quantitative analysis of fibrosis was performed using specific software.
Results: Capillary C4d depositions, which would be regarded diagnostic for AMR in cardiac allografts (in >50% of capillaries) were observed in 4 pts (in 2 DCM and ICM pts each), whilst C4d depositions in >10% of capillaries were observed in all but 3 pts. No correlations could be found between C4d depositions, quantity of CD68+/CD3+ inflammatory infiltrates, the degree of myocardial remodeling, taking into account quantity of collagen deposition, nor for underlying disease.
Conclusion: Our findings indicate that an activation of the classical complement pathway with interstitial capillary C4d depositions occurs frequently in the myocardium of patients with end-stage heart failure. Thus, capillary C4d depositions need to be considered thoroughly as a possible unspecific finding in the diagnostic setting of AMR in cardiac allografts
- © 2013 by American Heart Association, Inc.