Procalcitonin PCT detection and its clinical significance

I. Overview

PCT is a hormone-free calcitonin propeptide material consisting of 116 amino acids with a molecular weight of 13 KD. PCT has a half-life of 25 to 30 hours and is very stable in vitro. The plasma PCT content of healthy people is extremely low (<0.1 ng·ml-1=, 0.5 ng·ml-1 is considered to be the demarcation value for the diagnosis of infectious diseases.

PCT selectively responds to systemic bacterial infections, fungal infections, and parasitic infections, with no or only mild responses to aseptic inflammation and viral infection. Many scholars have found that PCT levels are abnormally increased when systemic bacteria, fungi, and parasites are infected. The degree of increase is related to the severity and prognosis of infection. In the differential diagnosis, prognosis, and efficacy of systemic bacterial infection and sepsis. Observation and other aspects have high clinical value. Monitoring of PCT levels is useful for life-threatening infectious disease processes and follow-up treatment options. Elevated PCT concentrations indicate that inflammatory responses are underway, using adequate antibiotics, inflammatory lesions, etc., PCT values Decline, to prove that the treatment plan is correct, the prognosis is good, and vice versa.

PCT provides help and support for the differential diagnosis of all inflammatory diseases of unknown etiology, such as bacterial and toxin-induced acute adult respiratory distress syndrome (ARDS); identification of biliary and toxin pancreatitis; bacterial and Identification of viral meningitis; identification of microbial-induced fever and non-bacterial fever, especially the diagnosis of fever (FOU), identification of viral infection or autoimmune disorders and acute bacterial infection under immunosuppressive conditions, fever Identification of the cause, such as tumor lysate or chemotherapy induced by tumors, bacteria or other infections, early diagnosis of neonatal and infant systemic bacterial infections and acute fever caused by sepsis; postoperative routine, including postoperative Infection warning and medication monitoring, postoperative treatment of resected infections (such as peritonitis, soft tissue infections), monitoring of peritonitis, anastomotic leakage and disease without typical abdominal symptoms; monitoring after organ transplantation, excluding acute bacteria before transplantation or Other infections, identification of acute organ rejection, acute viral, bacterial and fungal infections; long-term ICU patients and long Monitoring of patients with mechanical ventilation, monitoring the disease process and guiding treatment; monitoring high-risk patients, early access to information on complications and internal environment decline.

Many clinical studies have demonstrated that PCT is of great value in the diagnosis and guidance of treatment in different medical fields. Compared with the currently used diagnostic indicators, PCT provides additional information in the differential diagnosis and control of infection and severe inflammation. With the continuous deepening of clinical practice research and the continuous accumulation of clinical data, PCT as a routine indicator of systemic bacterial infection and sepsis assisted and differential diagnosis will become a consensus and will be widely used.

Second, PCT molecular biology structure

PCT is derived from a single copy gene (11P15,4) located on chromosome 11 (the same gene as the calcitonin gene-related peptide). The gene consists of 2800 base pairs, contains 6 exons and 5 introns, and the gene is about 7.6Kb in length. After transcription, PCT mRNA is generated by specific editing, and then translated into procalcitonin precursor (Pre-PCT). In the Golgi complex and secretory sac, a series of hydrolase acts to form PCT amino acid polypeptide (aminoPCT), calcitonin. (CT) and 21 amino peptides at the carboxy terminus (CT: CCP-1).

Third, serum PCT sources and possible biological mechanisms

Under normal conditions, human serum PCT content is extremely low, about 2.5pg/ml (using high performance liquid chromatography), while mature CT content is about 6.3 pg/ml. In patients with medullary thyroid tumors or other neuroendocrine tumors, serum PCT and its components are increased, and the relative content of components is also changed. In some patients with non-thyroid damage such as chronic renal failure, inhalation burns, acute bacterial infections, stroke, sepsis, etc., PCT and its components also increased, and some even increased exponentially, while CT increased slightly, indicating that the thyroid marrow was removed. In addition to PCT secretion and storage of PCT, there are still other cells that have these functions.

Possible biological mechanisms of elevated PCT: target cells (PBMCs, etc.) are secreted by PCT under the action of various LPS-related factors of LPS. This emergency secretion exceeds the post-cell transcriptional process (decomposed into aminoPCT, CT, by Pro-CT). CT: CCP-1) or post-conversion process lacks the necessary hydrolase, resulting in a doubling of the PCT observed in the experiment, while the CT level is unchanged or slightly increased.

Fourth, the detection method and the range of normal reference values

At present, in addition to time-consuming and easily automated gel chromatography and high performance liquid chromatography, the specific and sensitive analytical methods for detecting PCT are: double-antibody sandwich immunochemiluminescence (double-anti-sandwich method) and radioimmunoassay (RIA). ).

The double-antibody sandwich method uses a double monoclonal antibody, one of which acts as a capture antibody to directly bind to the PCT96-106 amino acid residue, i.e., the immature CT:CCP-1 portion, and the other as a tracer antibody directly binds to the PCT70-76 amino acid residue, ie, Mature CT molecules, synthetic PCT as a standard. The method is relatively specific and has no cross-reaction, and the detection is at least 10 pg·ml-1l, and the linear range of the standard curve is 10-60 pg·ml-1. The intra- and inter-assay coefficients of variation were 7c/o and 8c/o, respectively. This method has commercial reagents, which takes a short time and is easy to automate, but the method cannot detect PCT in normal human serum.

RIA uses a polyclonal antibody RIB7 specific for synthetic aminoPCT. RIB7 directly acts on the aminoPCT part of PCT, so RIA can detect both free PCT and combined PCT, as well as calcitonin gene-related precursor (Pro-CGRP). The sensitivity of this method is 4 Pg·ml-1. The linear range is 10-77pg·ml-1, and the binding free ratio of 50c/o is 140 pg·ml-1. This method can detect normal human serum PCT, so it is more sensitive than the double-anti-sandwich method. Another advantage is that the RIA and the patient's disease course are presented. Positive correlation (r=0.47, p=0.071). The disadvantage of RIA is that it takes a long time.

5. Application of PCT detection in different clinical departments

Hematology oncology

Severe infections are fatal complications in patients with immunosuppression and neutropenia caused by chemotherapy or bone marrow transplantation, and there are many causes of fever during chemotherapy. Fever is usually a symptom of a bacterial, viral or fungal infection, but sometimes it is a reaction to the drug during treatment. The fever caused by tumor cell lysis is more common, and the source of fever in most cases remains unclear. PCT helps to make a clear diagnosis of systemic infections caused by bacteria and fungi. Even in patients with chemotherapy, the PCT can reliably detect and assess whether there is a sepsis infection.

Patients with neutropenia often lack specific symptoms of inflammation. The performance of PCT in immunosuppressive and neutropenic patients was similar to that observed in patients without immunosuppression. Its diagnostic value has been significantly better than CRP and cytokines.

Bone marrow transplant patients or hematopoietic stem cell transplant patients have long-term physical and cellular immunodeficiency in both quantitative and qualitative conditions, which will mask serious systemic infections caused by bacteria, fungi, viruses and protozoa. Elevated PCT concentrations have a high diagnostic rate for bacterial systemic infections. If septic shock occurs after allogeneic transplantation, plasma PCT concentrations are extremely elevated, indicating a poor prognosis.

2. Anesthesiology

Postoperative sepsis infection and multiple organ failure remain the most common causes of death in the intensive care unit. The plasma PCT concentration of small and medium surgery is usually within the normal range. For major operations such as large abdominal surgery or thoracic surgery, the PCT concentration often increases within 1-2 days after surgery, usually 0.5-2.0 ng·ml-1, and occasionally more than 5 ng. · ml-1, which often drops to normal levels within a few days at a 24-hour half-life rate. Therefore, the high concentration or high level of PCT caused by infection after surgery is easy to identify.

12-24 hours after compound trauma, PCT moderately increased to 2.0 ng·ml-1, severe lung or chest trauma, PCT up to 5 ng·ml-1, and half-life rate if there is no infection complications To the normal range.

3. Internal medicine

Problems in medical intensive care are often centered around the diagnosis of infection and the differential diagnosis associated with infection. Whether the evaluation of the severity of inflammation and its treatment results is effective is a necessary prerequisite for an effective treatment plan.

PCT selectively responds to systemic bacterial infections, similar bacterial infections, and protozoal infections, with no or only mild responses to aseptic inflammation and viral infection. Therefore, PCT can be easily applied to the differential diagnosis of common diseases and syndromes in medical treatment, such as: differential diagnosis of infectious and non-infectious etiology of adult respiratory distress; necrosis and aseptic necrosis of pancreatitis Differential diagnosis; identification of fever during infection, such as cancer and blood disease patients receiving chemotherapy; differential diagnosis of acute autoimmune diseases and rheumatic diseases with systemic bacterial infection in patients receiving immunosuppressive agents; differential diagnosis of bacteria Meningitis and viral meningitis; for patients with neutropenic chemotherapeutic chemotherapy, whether there are life-threatening bacterial and fungal infections; for organ transplant recipients receiving immunosuppressive therapy, whether there are serious bacteria And fungal infections, as well as differential diagnosis for infection and transplant rejection.

4. Transplant surgery

Successful organ transplants are often challenged by complications like severe infections. In 31c/o patients, infection occurs within the first year after organ transplantation, and the symptoms of infection can be masked by acute and chronic rejection, so early and reliable diagnosis of infection during the rejection period cannot be made. Organ transplant patients use PCT testing to introduce early treatment to improve survival and shorten hospital stay.

PCT is used for the diagnosis of infection in organ transplant patients, and immunosuppressive therapy severely impairs the anti-infective ability of organ transplant patients. PCT can indicate the presence of a systemic infection as early as 2 hours after infection. Early infection PCT>0.1 ng·ml-1, sensitivity 77c/o, specificity 100c/o, monthly PCT concentration monitoring can be a reliable evaluation of the efficacy of anti-microbial therapy.

PCT is applied to organ rejection, and one of the main tasks of post-transplant monitoring is to clearly distinguish between infection and organ rejection. Since the release of PCT is not caused by acute or chronic organ rejection, high concentrations of PCT can be considered to be present. If the PCT concentration exceeds 10 ng·ml-1, 98c/o may be infected rather than organ rejection.

5. Neonatology

Many diseases have no specific manifestations in preterm infants and newborns. Hematological examinations and traditional laboratory indicators and acute phase proteins do not provide a reliable diagnosis of neonatal sepsis. The results of microbiological examinations take several days, and negative results do not rule out the presence of clinical infections and the associated high mortality rates. Compared with other inflammatory diagnostic indicators, PCT is an improved laboratory indicator that is highly sensitive and specific for the diagnosis of neonatal sepsis. PCT can also be used to evaluate treatment outcomes.

PCT age-dependent normal values ​​in preterm infants and neonates: PCT reached its physiological peak of 21 ng·ml-1 at 24-30 hours after birth, but the average was only 2 ng·ml-1. From the third day after birth, the PCT normal reference value is the same as that of adults.

PCT is a highly specific indicator of neonatal sepsis: premature infants and neonatal sepsis infections, PCT can make an earlier and more specific diagnosis than traditional methods, and its sensitivity and specificity for neonatal diagnosis can reach 100c / o.

6. Pediatrics

It is often difficult to distinguish different sources of infection in clinical practice of high fever in children. This problem especially affects the accurate diagnosis of patients who receive immunosuppressive therapy due to blood and tumor diseases. Moreover, many diseases are accompanied by secondary immunopathological changes, such as rheumatic fever, so it is difficult for children to distinguish them from primary bacterial infections.

PCT has a high sensitivity and specificity for the differential diagnosis of bacterial and viral infections. Because of the essential differences in the treatment of bacterial infections and viral infections, PCT can provide valuable information for the treatment of patients with non-specific infection symptoms.

Detection of proteins and cells in cerebrospinal fluid does not help to identify bacterial meningitis and viral meningitis in children, and there are significant cross-overs between many specific detection indicators. High concentrations of PCT occur only in bacterial meningitis; while viral meningitis PCT remains within the normal range (PCT is not detected in cerebrospinal fluid). The PCT concentration is monitored daily by time to provide a reliable assessment of treatment outcomes.

7. Surgery

Septicemia and multiple organ failure are postoperative fatal complications. Although modern medicine has made great progress, there are still no good strategies for this. Early and accurate diagnosis of sepsis infections that are not caused by the original disease or surgical trauma itself is the key to successful treatment.

PCT concentration is not affected by existing diseases such as cancer, allergy or autoimmune diseases. PCT is superior to other inflammatory factors such as CRP and cytokines. It is an objective and easy to detect indicator with unique diagnostic advantages. Even better than those with invasive, risky and high-cost diagnostic methods, such as fine needle aspiration biopsy.

降钙素原 PCT 检测及其临床意义

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