Background: Cerebrospinal fluid (CSF) leaks are potentially life-threatening conditions that can be diagnosed by detection of β(2)-transferrin using protein electrophoresis. Another less commonly available test is β-trace protein quantitation using immunoassay. The objectives of this study were to evaluate a new immunofixation-based β(2)-transferrin test for detection of CSF leaks and to compare it to an existing agarose gel electrophoresis test and β-trace protein immunoassay.
Methods: For method comparison, 63 consecutive samples from physician-ordered β(2)-transferrin tests were analyzed using two different electrophoresis methods, agarose gel fractionation followed by acid-violet staining, and high resolution agarose gel electrophoresis followed by β(2)-transferrin immunofixation. A subset of samples (16/63) were analyzed for β-trace protein. Results were compared against patient chart data for the presence of a CSF leak. Additional studies were performed to assess the stability, detection limit, and analytical specificity of the β(2)-transferrin immunofixation test.
Results: The β(2)-transferrin immunofixation test had a sensitivity of 100 % (40/40) and specificity of 71 % (12/17) for detection of CSF leaks. By comparison, the agarose gel test had a sensitivity of 87 % (35/40) and specificity of 94 % (16/17). β-trace protein had a sensitivity of 100 % (10/10) and specificity of 86 % (5/6). Serum and saliva could be differentiated from CSF by the β(2)-transferrin immunofixation test based on their migration patterns. However, whole blood samples appeared positive for β(2)-transferrin at a threshold of ~ 4 g/L hemoglobin. At a cut-off of 3 mg/L, β-trace protein was increased in 10/10 cases with documented CSF leak and in 1/6 patients without CSF leak.
Conclusions: Both the new immunofixation test for β(2)-transferrin and the β-trace protein were effective at detecting CSF leaks. Users of the β(2)-transferrin immunofixation test should be cautioned against interpreting samples with blood contamination.