**I. Overview**
Procalcitonin (PCT) is a hormone-free calcitonin precursor composed of 116 amino acids with a molecular weight of approximately 13 kDa. It has a half-life of 25 to 30 hours and exhibits high stability in vitro. In healthy individuals, plasma PCT levels are extremely low (<0.1 ng/mL), with 0.5 ng/mL considered the threshold for diagnosing infectious conditions.
PCT demonstrates a selective response to systemic bacterial, fungal, and parasitic infections, with minimal or no reaction to aseptic inflammation or viral infections. Clinical studies have shown that PCT levels significantly increase during such infections, and the degree of elevation correlates with the severity and prognosis of the condition. This makes PCT a valuable tool in differential diagnosis, prognosis assessment, and treatment monitoring for bacterial infections and sepsis. Monitoring PCT levels helps identify life-threatening infections and guide appropriate therapeutic strategies. Elevated PCT indicates ongoing inflammatory responses, and its decline after antibiotic administration suggests effective treatment and a favorable prognosis.
PCT plays a crucial role in diagnosing various inflammatory diseases of unknown origin, including bacterial and toxin-induced acute respiratory distress syndrome (ARDS), biliary and toxic pancreatitis, bacterial and viral meningitis, microbial-induced fever, and non-bacterial fever. It is especially useful in diagnosing fever of unknown origin (FUO), distinguishing between viral infections and autoimmune disorders under immunosuppressive conditions, and identifying the cause of fever in patients with tumors or post-chemotherapy. Additionally, PCT aids in early detection of neonatal and infant systemic bacterial infections, sepsis-related fevers, and post-surgical complications like peritonitis or anastomotic leakage.
In intensive care units (ICUs), PCT monitoring helps track disease progression and guide treatment for long-term ventilated patients. It also assists in identifying complications and changes in the internal environment in high-risk individuals. With growing clinical research and data accumulation, PCT is becoming a widely accepted biomarker for diagnosing and managing systemic bacterial infections and sepsis.
**II. Molecular Biology Structure**
PCT originates from a single-copy gene located on chromosome 11 (11p15.4), which is the same gene responsible for calcitonin gene-related peptide (CGRP). The gene spans 2800 base pairs, contains six exons and five introns, and is approximately 7.6 kb in length. Following transcription, PCT mRNA undergoes specific editing and is translated into procalcitonin precursor (Pre-PCT). In the Golgi apparatus and secretory vesicles, a series of hydrolases process Pre-PCT into PCT, which includes the amino-terminal fragment (aminoPCT), calcitonin (CT), and a 21-amino acid C-terminal fragment (CT: CCP-1).
**III. Serum PCT Sources and Possible Biological Mechanisms**
Under normal conditions, serum PCT levels are very low, around 2.5 pg/mL (measured by high-performance liquid chromatography), while mature CT is about 6.3 pg/mL. In patients with medullary thyroid cancer or other neuroendocrine tumors, PCT and its components are elevated, and their relative composition may change. In cases of non-thyroid conditions such as chronic kidney failure, burns, acute bacterial infections, stroke, or sepsis, PCT levels can rise significantly, sometimes exponentially, while CT increases only slightly. This suggests that PCT is not exclusively produced by thyroid cells but may also originate from other tissues.
The mechanism behind elevated PCT involves the release of PCT from target cells, such as peripheral blood mononuclear cells (PBMCs), under the influence of lipopolysaccharide (LPS)-related factors. This rapid secretion exceeds the typical post-translational processing (which breaks down PCT into aminoPCT, CT, and CCP-1), leading to higher observed PCT levels compared to CT, which remains stable or slightly increased.
**IV. Detection Methods and Normal Reference Ranges**
Currently, common methods for detecting PCT include time-consuming gel chromatography and high-performance liquid chromatography. More specific and sensitive techniques include double-antibody sandwich immunochemiluminescence and radioimmunoassay (RIA).
The double-antibody sandwich method uses two monoclonal antibodies: one acts as a capture antibody binding to PCT residues 96–106 (the immature CT:CCP-1 region), while the other serves as a tracer antibody targeting PCT residues 70–76 (mature CT). This method offers high specificity, no cross-reaction, and a detection limit of at least 10 pg/mL. Its linear range is 10–60 pg/mL, with intra- and inter-assay coefficients of variation of 7% and 8%, respectively. However, it cannot detect PCT in normal human serum.
RIA employs a polyclonal antibody (RIB7) specific for synthetic aminoPCT. Since RIB7 binds to the aminoPCT portion of PCT, this method can detect both free and bound PCT, as well as the calcitonin gene-related peptide precursor (Pro-CGRP). RIA has a sensitivity of 4 pg/mL, a linear range of 10–77 pg/mL, and a binding free ratio of 50% at 140 pg/mL. It can detect PCT in normal serum, making it more sensitive than the double-antibody method. Additionally, RIA shows a positive correlation with the patient’s disease course (r = 0.47, p = 0.071). However, it is slower compared to other methods.
**V. Application of PCT in Different Clinical Departments**
**Hematology/Oncology**
Severe infections are a major complication in immunosuppressed patients undergoing chemotherapy or bone marrow transplantation. Fever is often due to bacterial, viral, or fungal infections, but can also be drug-related. PCT helps distinguish between these causes and assesses the presence of sepsis. In neutropenic patients, PCT outperforms CRP and cytokines in diagnostic accuracy.
**Anesthesiology**
Postoperative sepsis and multiple organ failure remain significant causes of ICU mortality. PCT levels typically rise after major surgeries and return to baseline within days. In trauma patients, PCT increases moderately and returns to normal if no infection occurs.
**Internal Medicine**
In critical care settings, PCT is used to differentiate between infectious and non-infectious causes of inflammation. It is particularly useful in diagnosing conditions such as ARDS, pancreatitis, and meningitis.
**Transplant Surgery**
Organ transplant recipients are at high risk for infections, which can be masked by rejection symptoms. PCT helps distinguish between infection and rejection, with high concentrations indicating infection rather than rejection.
**Neonatology**
PCT is a highly specific marker for neonatal sepsis. It peaks at 21 ng/mL shortly after birth but declines to adult levels by day three. It provides earlier and more accurate diagnosis than traditional methods.
**Pediatrics**
In children, PCT aids in differentiating bacterial from viral infections, especially in those receiving immunosuppressive therapy. It is also useful in diagnosing meningitis and monitoring treatment response.
**Surgery**
PCT helps identify sepsis after surgery, guiding early intervention. It is more reliable than CRP and less invasive than procedures like fine needle aspiration.
PCT continues to gain recognition as a key biomarker in the diagnosis and management of infectious diseases across multiple medical specialties.
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