Background
Despite well-described analytical effects of autoantibodies against cardiac troponin (cTn) I on experimental assays, no study has systematically examined their impact on cTn assays in clinical use. We determined the effects of endogenous antibodies on 5 different cTnI assays and a cTnT assay.
Methods
cTn was measured by 6 methods: Siemens hs-cTnI Centaur, Siemens hs-cTnI Vista, Abbott hs-cTnI Architect, Beckman hs-cTnI Access, Beckman cTnI Access, and Roche hs-cTnT Elecsys. Measurements were repeated on 5 assays (all except Siemens hs-cTnI Vista) following immunoglobulin depletion by incubation with protein A. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered positive for macro-cTnI. Protein A findings were validated by gel filtration chromatography and polyethylene glycol precipitation.
Results
In a sample of 223 specimens selected from a community laboratory that uses the Siemens hs-cTnI Centaur assay and from which cTn was requested, 76% of samples demonstrated increased cTnI (median, 88 ng/L; interquartile range, 62–204 ng/L). Macro-cTnI was observed in 123 (55%) of the 223 specimens. Comparisons of cTnI assays markedly improved once patients with macro-cTnI were removed. Passing-Bablok regression analysis between hs-cTnI assays demonstrated different slopes for patients with and without macro-cTnI. In patients with macro-cTnI, 89 (72%) showed no effect on the recovery of cTnT, whereas 34 (28%) had reduced recovery of cTnT. The proportion of results above the manufacturers' 99th percentile varied with the cTn assay and macro-cTnI status.
Conclusion
We suggest that the observed discrepancy between hs-cTnI assays may be attributed in part to the presence of macro-cTnI.
Postmortem tryptase is a useful biochemical test to aid the diagnosis of anaphylaxis. Multiple perimortem and postmortem factors have been documented to cause an elevation in postmortem tryptase level. One factor that was recently recognized to have an impact on postmortem tryptase level is correct sampling technique. A recent study recommended aspirating blood samples from a clamped femoral/external iliac vein to be used for reliable postmortem tryptase analysis. This study sampled 120 consecutive nonanaphylactic deaths in which all the peripheral bloods were sampled as recommended. Postmortem interval, resuscitation, different nonanaphylactic causes of death, sex, and age did not show any statistical significant relation to postmortem tryptase level in Student t test, Pearson correlation, and univariate and multivariate analyses. The mean (SD) postmortem tryptase level was 8.4 (5.2) μg/L (minimum, 1.0 μg/L; maximum, 36.1 μg/L; median, 7.3 μg/L). Using nonparametric methods, the postmortem tryptase reference range in nonanaphylactic death was established as <23 μg/L (97.5th percentile).
Analytical interference identified on one immunoassay should raise the possibility of other affected results. Characterization of interference may help to identify other potentially affected immunoassays. In the case of anti-streptavidin antibodies, the pattern of interference mimics that due to biotin ingestion. However, the degree of interference varies between individual assays and between patients.
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