The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation.

Plasma levels of tumor necrosis factor-alpha were measured in 50 adult patients following orthotopic liver transplantation. The mean (+/- SEM) plasma concentration of TNF-alpha was significantly higher in patients experiencing a rejection episode (941 +/- 83 pg/ml) than in those with a stable clinical course (240 +/- 6 pg/ml; P = 0.0001). Peak levels of TNF-alpha were usually found at the time of clinically diagnosed rejection, although elevated levels were observed 1-2 days earlier. First-week peak TNF-alpha levels were significantly higher in patients who suffered graft loss (2146 +/- 788 pg/ml) than in those who were discharged from the hospital without clinical evidence of rejection (581 +/- 93 pg/ml; P = 0.004). TNF-alpha levels were not correlated with white blood cell count (r2 = 0.004), cyclosporine levels (0.01), serum creatinine (0.002), serum bilirubin (0.05), serum SGOT (0.03), or SGPT (0.05). TNF-alpha levels were not elevated in four cases of viral hepatitis occurring after transplantation. We conclude that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. First-week TNF-alpha levels are also useful predictors of long-term graft outcome. Further investigation is required to determine whether this monokine is important in the actual pathogenesis of allograft rejection.

Detection of sialylated LewisX antigen in cancer sera using a sandwich radioimmunoassay.

A monoclonal antibody directed against sialylated LewisX (SLEX) was tested with the serum of 615 cancer patients, 166 patients with non-malignant diseases, and 136 normal persons. The SLEX antibody reacted with the sera of the cancer patients in the following percentages: 29% lung, 19% breast, 12% ovary, 25% colorectal, 13% head and neck, and 13% miscellaneous. SLEX was positive for 22% of stages III and IV (late-stage) cancers as compared with 5% early-stage tumors. Among 80 patients with adenocarcinoma of the lung in the late stages, 45% were positive for SLEX. However, among 54 patients having squamous-cell lung cancer in the late stages, 15% were positive. In 25 cases of small-cell lung cancer, 24% were positive. Among patients who had measurable lung cancer, 4/7 with adenocarcinoma over 3 cm in diameter were positive whereas 0/16 patients with tumors under 3 cm were positive. Four patients who had tumor regression showed a more than 50% decrease in SLEX values whereas in 7 patients with progressive tumors, a more than 50% increase in SLEX levels was found. When tested simultaneously with CEA, SLEX produced positive reactions with the sera of some patients who were negative for CEA. The reaction pattern was distinct, indicating that another antigen was being detected. When used in combination, the percentage of sera that were positive increased. We conclude that the use of SLEX is useful for monitoring of cancer patients.

Detection of differentiation antigens by use of monoclonal antibodies.

Various monoclonal antisera placed at appropriate dilutions in a microcytotoxicity typing tray can be used to characterize different cell types with the aid of a simple 2-h microcytotoxicity test. With this simple assay, T and B lymphocytes, granulocytes, monocytes, blast cells, and platelets can readily be distinguished. In addition, spleen cells contained 25-50% T cells, half of which expressed Ia antigens. The presence of Ia-bearing T cells in peripheral blood lymphocytes of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients can also be detected using this cytotoxicity tray.