title: Urinary thromboxane B2 in cardiac transplant patients as a screening method of rejection.
abstract: Noninvasive methods for regular monitoring of cardiac transplant patients for acute rejection are preferable to the only currently accepted method involving frequent endomyocardial biopsies. Thromboxane A2 (TXA2) 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 histocompatibility class II expression on antigen presenting cells. Experimentally increased urinary excretion of TXA2 metabolites is associated with cardiac transplant rejection. We therefore compared urinary immunoreactive thromboxane B2 (i-TXB2) levels to the rejection score of the endomyocardial biopsies. In addition we graded the degree of activated lymphocytes in peripheral blood. Urinary i-TXB2 was significantly higher in patients 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 endomyocardial biopsy indicated rejection, was also significantly higher than in the non-rejecting group. Increased levels of urine i-TXB2 were associated with increased biopsy scores. Circulating activated lymphocytes was also significantly increased in patients with moderate/severe 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-TXB2 is associated with increased endomyocardial biopsy scores (acute rejection scores) and blood lymphocyte activation. Thus we conclude that urine i-TXB2 may be of potential value as a diagnostic screening test for helping identify cardiac transplant patients undergoing acute rejection.
authors.affiliation: Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: N M
authors.initials: NM
authors.lastname: Katz
authors.forename: E A
authors.initials: EA
authors.lastname: Lefrak
authors.forename: M L
authors.initials: ML
authors.lastname: Foegh
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000652:urine*; D016027:Heart Transplantation; D006801:Humans; D008213:Lymphocyte Activation; D012680:Sensitivity and Specificity; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000652:urine*
chemical_list: D013929:Thromboxane B2