URINARY THROMBOXANE B-2 IN CARDIAC TRANSPLANT PATIENTS AS A SCREENINGMETHOD OF REJECTION

Noninvasive methods for regular monitoring of cardiac transplant patie nts for acute rejection are preferable to the only currently accepted method involving frequent endomyocardial biopsies. Thromboxane A(2) (T XA(2)) is synthesized in large amounts by monocytes/macrophages during organ graft rejection. It enhances T-lymphocyte clonal expansion and cytotoxic function as well as upregulating the major histocompatibilit y class II expression on antigen presenting cells. Experimentally incr eased urinary excretion of TXA(2) metabolites is associated with cardi ac transplant rejection. We therefore compared urinary immunoreactive thromboxane B-2 (i-TXB2) levels to the rejection score of the endomyoc ardial biopsies. In addition we graded the degree of activated lymphoc ytes in peripheral blood. Urinary i-TXB2 was significantly higher in p atients exhibiting medium to severe rejection than in patients without rejection (1236 +/- 372 vs. 526 +/- 57 pg/mL). The urine i-TXB2 (704 +/- 48 pg/mL) of all patients who participated in this study, whose en domyocardial biopsy indicated rejection, was also significantly higher than in the non-rejecting group. Increased levels of urine i-TXB2 wer e associated with increased biopsy scores. Circulating activated lymph ocytes was also significantly increased in patients with moderate/seve re rejection compared to patients with no rejection (66 +/- 11 vs. 39 +/- 4 per mm (3)) (p < 0.01). Further, this study shows that urine i-T XB2 is associated with increased endomyocardial biopsy scores (acute r ejection scores) and blood lymphocyte activation. Thus we conclude tha t urine i-TXB2 may be of potential value as a diagnostic screening tes t for helping identify cardiac transplant patients undergoing acute re jection.