QUANTIFICATION OF CELL-PROLIFERATION IN THE INFLAMMATORY INFILTRATE OF ENDOMYOCARDIAL BIOPSIES AFTER CARDIAC TRANSPLANTATION - AN AID IN DIAGNOSIS OF SEVERE ACUTE REJECTION

The histological grading of endomyocardial biopsies still represents t he gold standard in the diagnosis of cardiac allograft rejections. Sev ere acute rejections (grade 3A/3B, ISHLT) after heart transplantation require immediate high-dose immunosuppressive therapy. The histomorpho logical differentiation to the rejection requiring no therapy (grade 2 ) is often difficult. The aim of this study is the improvement of the diagnostic identification of therapy-requiring rejections using quanti fication of cell proliferation in the inflammatory infiltrate of biops ies. 322 consecutive endomyocardial biopsies from 48 heart allograft r ecipients were immunohistochemically investigated using the monoclonal antibody MIB-1 binding selectively to the proliferation associated an tigen Ki 67. Fifty percent of all biopsies showed cell proliferation: 47.0 % in absent or mild rejection (0, 1A, 1B) compared to 88.0 % in m oderate to severe rejection (2, 3A/3B) (p < 0.01). Proliferating cells were arranged in a focal or perivascular pattern in 66.0 % and diffus e in 34.0 %. The quantity of proliferating cells per biopsy - but not the pattern - correlated with the grade of rejection: 0.7 % in grade 0 , 1.4 %/5 % in 1A/1B, 8.5 % in grade 2 up to 18.7 % in 3A/3B, and 2.7 % in R1 (p < 0.01, c(corr) = 0.65). The amount of proliferating mononu clear cells in the inflammatory infiltrate in acute cardiac allograft rejection is proportional to the severity of the rejection and thus an aid in the difficult histological differentiation of grade 3A/3B.