Table 1.
Assay | Source | Type of test | Status | Peptides identified |
Low assay standard |
Functional sensitivity |
Mean of healthy controlsa |
Assay time | Comments |
---|---|---|---|---|---|---|---|---|---|
(pg·mL−1) | (pg·mL−1) | (pg·mL−1) | |||||||
NProCT | Becker et al. | elisa | Research | ProCT and NProCT | 10 | 20 | 33b | 16–18 h | Highly sensitive, quantitates most normals; equipment readily available Slow; requires plate reader |
ProCa-S | BRAHMS | ILMA | Research | ProCT and CT : CCP-I | 5 | 20 | 31 | 3 h | The most sensitive ILMA assay, rapid assay Requires luminometer |
PCT sensitive | BRAHMS | ILMA | Research | ProCT and CT : CCP-I | 5 | 50 | 13 | 3 h | Highly sensitive; rapid Requires luminometer |
QPCT | BRAHMS | Solid-phase | Commercial | ProCT and CT : CCP-I | (500) | (500) | (500) | 5 min | Rapid bedside test needing no equipment Semiquantitative test; provides determinations only within very broad ranges |
LUMItest | BRAHMS | ILMA | Commercial | ProCT and CT : CCP-I | 80 | 500 | 235 | 2 h 45 min | The most widely used test to date; rapid Relatively insensitive; cannot detect mild elevations or mild variations; expensive to do single determinations; requires luminometer |
KRYPTOR | BRAHMS | TRACE | Commercial | ProCT and CT : CCP-I | 20 | 60 | 53 | Initial sample: 50 min Stat sample: 25–45 minc | Sufficiently sensitive for most purposes; readily detects daily changes, ideal for a large number of determinations; and hence inexpensive for this usage Most appropriate for large-volume usage as in hospitals, large infectious disease services, intensive care units or emergency rooms Requires Kryptor machine |
Note:As shown above, no currently available commercial assay measures exclusively procalcitonin. All assays detect at least one other constituent of this prohormone. High-performance liquid chromatography studies of calcitonin gene peptides extracted from concentrated normal human serum reveal very low levels of ProCT (2.5 pg·mL−1) plus its component peptides (NProCT, CT, CCP-I and CT : CCP-I) (Snider et al., 1997). In hyperprocalcitonemic states, procalcitonin and its constituent peptides all may be increased to varying extent from patient to patient. Other than the hyperprocalcitonaemia that is due to secretion from a neuroendocrine tumour, the amidated free CT in patients with sepsis, infection or systemic inflammation remains low. CT is not measurable in any of the above assays. For simplicity of expression, all these above assays are now referred to by investigators as ‘procalcitonin’ assays.
The discrepancy between functional sensitivity and healthy control values (i.e. LUMItest, PCT sensitive, KRYPTOR) implies considerable uncertainty of the values in this population. Because none of these cited assays are capable of measuring the actual values of ProCT in sera from healthy controls, the authors recommend that investigators not try to make comparisons between data points below the functional sensitivity of the assays because such comparisons are likely to be unreliable.
This level is 90% aminoprocalcitonin, based on chromatography studies. The actual mean level of ProCT in healthy controls is <4 pg·mL−1. ProCT + CT : CCP-I < 5 pg·mL−1 (Snider et al., 1997).
The initial sample time includes the time required for powering up the equipment; performing the daily maintenance; and running the calibrators, control samples and the first sample. During the week, the machine may be left on and the calibrators need to be run only once. The time required for daily maintenance is less than 20 min. Additional samples loaded into the Kryptor machine along with the first sample require 1–2 min per sample; thus, for example, five additional samples can be measured within 5–10 min. The stat sample time shown above is the time required to measure a single sample that is loaded by itself after starting the machine. This includes the time that may be required for the automatic dilution and recount of a sample which contains a concentration of ProCT > 50 ng·mL−1.
ProCT, procalcitonin; NProCT, aminoprocalcitonin; CT : CCP-I, the conjoined peptide consisting of calcitonin + calcitonincarboxypeptide I (see Snider et al., 1997); elisa, enzyme-linked immunosorbent assay; ILMA, immunoluminometric assay; TRACE, time-resolved amplified cryptate emission.