Abstract

Objectives: Aim of this study was to find features characteristic for steroid resistant cellular rejection (SRR) of the transplanted heart, using phenotypic identification of cells creating infiltrates in endomyocardial biopsies (EMBs) obtained before and after high dose steroids treatment. Methods: 146 heart transplant recipients, treated with cyclosporine-A, azathioprine and prednisone, were taken under consideration. EMB results‡3A (ISHLT) were considered significant rejection, requiring treatment with 1g iv. methylprednizolone for 3 days followed by oral prednisone. SRR was diagnosed in case of increased grade of rejection in control EMB, lack of improvement in 2 consecutive EMBs or increasing hemodynamic compromise. SRR was found in 15 pts. (study group). Control group consisted of remaining 131 pts. Paraffin-embedded blocks containing EMB samples from 9 pts. from study group and randomly chosen14 pts. from control group were used (2 EMBs per pt.). Significant rejection was present in the first EMB, the second EMB was performed 7 days after beginning of the treatment. In the study group, first 2 EMBs creating a sequence of SRR were analysed. Following antigens were identified: CD45RO (T-cells), CD8 (cytotoxic T-cells), CD20 (B-cells), and CD95 (marker of apoptosis). DR expression and macrophages presence were also quantified. Results: CD45RO was predominant phenotype before and after treatment in both groups. Higher quantity of CD20 cells were observed in study group, however its number increased after treatment in control group. CD8-cells and macrophages were present in low amounts, that did not react to treatment. CD95 positive cells were present only in 3 EMBs. None of above differences was statistically significant. DR expression staining showed no difference either in biopsies taken before steroid treatment or after completing of high dose steroid therapy. Conclusion: Phenotype identification of cells infiltrating myocardium of the transplanted heart was not sufficient to predict or characterise steroid resistant rejection.

Keywords: Heart Transplantation, Steroid Resistant Acute Cellular Rejection, Endomyocardial Biopsy, Cellular Infiltrate, Lymphocytes Phenotyping