Antibody-mediated rejection in human cardiac allografts: histopathological and immunohistochemical study

Objective To observe the pathologic features on cardiac allograft and to test archived endomyocardial biopsy specimens for antibody-mediated rejection specific marker-C4d deposition and its characteristics by using immunoperoxidase (IP) techniques. Methods From January 2003 to December 2007,10 recipients underwent orthotopic cardiac transplantation and 17 specimens of endomyocardial biopsy were obtained either for a protocol basis (generally at 1 st month,3rd month,1st year and 2nd year post-transplant) and on immediate clinical indications.All specimens of endomyocardial biopsy were collected for histopathological examination and C4d immunohistochemical staining,simultaneously. All pathological diagnoses were done according to 2004 International Society for Heart and Lung Transplantation (ISHLT) recommendation working formulation and AMR Schema,and C4d staining intensity were graded and recorded as 0 to 3 +.Results Except 1 specimen unqualified,all 16 consecutive specimens of endomyocardial biopsy were qualified.There were 4 cases of acute T cell-mediated rejection (all graded 1 ),2 cases of Quilty lesion,and 7 cases of antibody-mediated rejection,who were documented according to ISHLT Schema and C4d deposition.Meanwhile,there were 6 cases showing evidence of antibody-mediated rejection without concurrent acute cellular rejection and only one case concordant with acute T cell-mediated rejection.One case of antibody-mediated rejection died 20 months posttransplantation due to combined transplant coronary artery disease (TCAD). The C4d in the cardiac allograft was deposited in microvasculature diffusively.Conclusion Antibody-mediated rejection is an important clinical entity following orthotopic heart transplantation and is difficult to diagnosis except to perform endomyoeardial biopsy.Immunoperoxidase staining for C4d is a sensitive and specific technique for detecting one marker of antibody-mediated rejection. Key words: Heart transplantation;  Antibody-mediated rejection;  Complement C4d ;  Pathology