GRANZYME-B AND PERFORIN CAN BE USED AS PREDICTIVE MARKERS OF ACUTE REJECTION IN HEART-TRANSPLANTATION

We have investigated perforin and granzyme B expression in graft-infil trating lymphocytes of patients who underwent heart transplantation. T hose proteins are commonly present in the cytoplasmic granules of cyto toxic T lymphocytes and are released upon effector-target cell interac tion. From 28 patients 103 endomyocardial biopsies were obtained and e xamined by histology and immunocytochemical analysis using relevant mo noclonal antibodies. We found that ''high'' biopsy histological grades were associated with perforin and granzyme B expression in graft-infi ltrating lymphocytes of patients with acute severe rejection crisis. I n contrast, these markers were not detected in patients without reject ion or during graft stabilization. Interestingly, in patients with mil d rejection and ''low'' histological grades, two groups could be disti nguished with a differential expression of the two intracytoplasmic pr oteins. The presence of perforin and granzyme B-expressing cells was f ound to be predictive of rapid progression to severe rejection, so tha t this situation required additional treatment; in contrast, their abs ence seemed to correlate with a good graft outcome without additional treatment. Moreover, perforin and granzyme B expression seemed to be d own-regulated by immunosuppressive drugs, which coincided with graft s tabilization. In conclusion, our data suggest that detection of granzy me B and perforin in graft-infiltrating lymphocytes might be helpful f or routinely monitoring heart transplant patients.