β2-Microglobulin, which is associated with HLA class 1 antigens, was assayed in bile and serum from 19 patients following 22 liver transplants. Serum levels were elevated in all posttransplant patients irrespective of the presence of rejection. In contrast, biliary levels were significantly higher during episodes of acute rejection compared with posttransplant cholangitis (p < 0.01), stable graft function (p < 0.0001) and nontrans-plant samples (p < 0.0001). When bile/serum ratios were studied, the difference between the rejection and the other groups was even more significant, and if a ratio of 0.2 was considered diagnostic of rejection, the test had a sensitivity of 96%, a specificity of 87% with an accuracy of 90%. Therefore, these results suggest that the measurement of bile/serum ratios of β2-microglobulin following liver transplantation may be useful in diagnosing acute rejection.
When bile/serum ratios of β2-microglobulin were compared with those for other proteins, there was strong evidence to suggest that local release accounted for most of the increased biliary β2-microglobulin during rejection. These results provide further evidence that HLA class 1 antigens on the biliary epithelium may be important in liver allograft rejection.