Procalcitonin Technotes

Procalcitonin (PCT) is a small protein (~13 kDa) that is synthesized by the C-cells of the thyroid glands. It is considered to be the main marker of disorders that are accompanied by systemic inflammation and sepsis.

PCT is encoded by the CALC-1 gene and it is the precursor of the calcitonin hormone. It is produced from a 141 amino acid long pre-procalcitonin. After removal of the signal peptide (amino acids 1-25), the 116 amino acid long PCT undergoes successive cleavages to form three molecules: N-terminal fragment (N-terminal PCT, 57 amino acid residues (a.a.r.)), calcitonin (32 a.a.r.) and katacalcin (21 a.a.r.) (Fig. 1).

PCT belongs to a family of related proteins (the CAPA peptides family), which also includes calcitonin, the calcitonin gene-related peptides I and II, amylin and adrenomodulin.

PCT in diagnostics

In 1993, an elevated level of PCT in patients with a system infection of bacterial origin was reported for the first time (1). It was shown that “inflammatory” PCT is not produced in C-cells, but rather in all parenchymal tissues and the differentiated cell types (2-4). PCT is a good marker of bacterial infection because its level in the blood of normal subjects is very low and due to the fact that viral infections cause only a minor increase in PCT concentration. In addition, the diagnostic value of PCT is further supported by the close correlation between PCT concentration and the severity of inflammation (1, 5).
In some cases, an increase in PCT concentration may be induced by factors independent of sepsis and infection. Surgery, polytrauma, heat shock, burn injuries, and cardiogenic shock also lead to an increase in the PCT level (1). Furthermore, the importance of monitoring the PCT level changes following cardiac surgery or heart transplantation for differentiating acute graft rejection from bacterial or fungal infections has been confirmed in multiple studies (5).

Assay development and pair recommendations

For the development of PCT immunoassays, Hytest offers monoclonal antibodies (mAbs) that are specific to different fragments of the PCT molecule: N-terminal fragment of PCT, calcitonin, and katacalcin. These mAbs can be used for the detection of the full-length or partially processed PCT molecule by using pairs of antibodies that are specific to different parts of PCT. The specificity of antibodies and the recommended capture-detection pairs for sandwich immunoassays are shown in Table 1. In addition to the mAbs, we also have a polyclonal PCT antibody that can be used for PCT-specific immunoassay development. Hytest also offers a recombinant, full-length PCT antigen that can be used as a calibrator in PCT or calcitonin immunoassays.

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