Isolation and characterization of serum procalcitonin from patients with sepsis

Weglöhner, Wolfgang; Struck, Joachim; Fischer-Schulz, Christina; Morgenthaler, Nils G.; Otto, Albrecht; Bohuon, C; Bergmann, Andreas

doi:10.1016/s0196-9781(01)00541-1

Cited by 59 publications

(32 citation statements)

References 14 publications

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“…PCT is a precursor peptide of the hormone CT and is also referred to as being the prototype of hormokine mediators [13]. After translation from CT mRNA, PCT is cleaved enzymatically into smaller peptides, to finally yield the 32-amino acid mature CT [14,15]. The CALC-I gene, by alternative processing of the primary RNA transcript, gives rise to two different socalled mature peptides: CT and CGRP-I [2].…”

Section: Calcitonin Peptides Are Prototypes Of Hormokinesmentioning

confidence: 99%

Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators

Christ‐Crain¹,

Müller²

2007

European Respiratory Journal

220

149

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Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term ''hormokine'' encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.

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Section: Calcitonin Peptides Are Prototypes Of Hormokinesmentioning

confidence: 99%

Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators

Christ‐Crain¹,

Müller²

2007

European Respiratory Journal

220

149

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“…Initial analyses using size-exclusion chromatography indicated that circulating PCT in sepsis patients has the theoretically-expected size of 116 amino acids (1 ), but there were also indications of the presence of breakdown products. A more detailed mass-spectrometric analysis of affinity-purified serum PCT of sepsis patients identified a molecule truncated at the N-terminus (PCT3-116) as the principal circulating PCT species (19 ), and DPPIV was identified as the protease that converts PCT1-116 to . Up to now, however, the complexity of such analysis has precluded large-scale and routine measurement of samples.…”

Section: Discussionmentioning

confidence: 99%

“…The primary translational product of CALCA, preprocalcitonin, is initially cleaved by the signal peptidase, resulting in the 116 amino acids that make up procalcitonin (PCT1-116). At a later time, the first 2 N-terminal amino acids of PCT1-116 can be cleaved off by dipeptidyl peptidase IV (DPPIV), leading to desAla-Pro-PCT (des-Alanin-Prolin-Procalcitonin; PCT3-116, which lacks the first 2 amino-terminal amino acids) (19,20 ). PCT1-116 and PCT3-116 might have different functional properties and different half-life times in vivo, which could potentially be translated into diagnostic applications superior to those available with present-day PCT assays.…”

mentioning

confidence: 99%

Method for the Selective Measurement of Amino-Terminal Variants of Procalcitonin

Struck¹,

Strebelow²,

Tietz³

et al. 2009

Clinical Chemistry

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Background: Procalcitonin (PCT) is an established marker for diagnosing and monitoring bacterial infections. Full-length PCT [116 amino acids that make up procalcitonin (PCT1–116)] can be truncated, leading to des-Ala-Pro-PCT (des-Alanin-Prolin-Procalcitonin; PCT3–116). Current immunoassays for PCT (“total PCT”) use antibodies directed against internal epitopes and are unable to distinguish amino-terminal PCT variants. Here we describe the development of monoclonal antibodies recognizing the amino-termini of PCT1–116 and PCT3–116 and their use in the selective measurement of these PCT species. Methods: With newly developed monoclonal antibodies against the amino-termini of PCT1–116 and PCT3–116, and an antibody against the katacalcin moiety of PCT, we developed and characterized immunoluminometric assays for the 2 PCT peptides. We comparatively assessed the kinetics of PCT variants in a human endotoxemia model. Results: Monoclonal antibodies against the amino-termini of PCT1–116 and PCT3–116 showed <1% cross-reactivity with other PCT-related peptides. The sandwich assays for PCT1–116 and PCT3–116 had functional assay sensitivities of 5 and 1.2 pmol/L, respectively, and exhibited recoveries within 20% of expected values. Plasma PCT1–116 was stable for 6 h at 22 °C and 24 h at 4 °C, and PCT3–116 was stable for at least 24 h at both temperatures. During experimental endotoxemia in healthy people, both PCT1–116 and PCT3–116 increased early in parallel with total PCT, but further increases in PCT1–116 were significantly slower than for PCT3–116 (P = 0.0049) and total PCT (P = 0.0024). Conclusions: The new assays selectively measure PCT1–116 and PCT3–116. Both PCT species increase early during endotoxemia but differ in their kinetics thereafter. The selective measurement of PCT species with different in vivo kinetics may be useful in improving PCT-guided therapies.

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“…In addition, CRP level measured by the standard technique may not detect low-grade inflammation, especially in Japanese patients with CKD [26] . Procalcitonin (PCT), a precursor of calcitonin and a polypeptide of 116 amino acids (molecular weight, 13 kDa), is a specific biomarker of bacterial infection [27] . Serum PCT (sPCT) has been reported to increase during bacterial infections in patients with CKD [28] .…”

Section: Chronic Inflammation and Infection In Patients With Ckdmentioning

confidence: 99%

Neutrophil/lymphocyte ratio: A promising prognostic marker in patients with chronic kidney disease

Kato

Abe²,

Lindholm³

et al. 2015

Inflamm Cell Signal

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Chronic kidney disease (CKD), especially end-stage renal disease (ESRD), is associated with high morbidity and mortality due to cardiovascular disease (CVD) and infection, two common complications of ESRD that may be related, in part, to chronic inflammation and protein-energy wasting (PEW). Recently, in a Japanese prospective cohort study, we reported that there was significantly higher risk for CVD-related events in CKD patients with an increased neutrophil/lymphocyte ratio (NLR) at the start of their dialysis therapy. Because higher neutrophil count reflects inflammation and lower lymphocyte count may reflect malnutrition, NLR is hypothesized to be a more sensitive index than other existing inflammatory markers for detecting those at high risk for CVD-related events. This research highlight describes the potentials of NLR as a prognostic marker in patients with CKD. Although further studies are required to better understand its value as prognostic tool in clinical practice, current data suggest that NLR may be a useful and inexpensive marker for identifying CKD patients at high risk for CVD-related complications.

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Isolation and characterization of serum procalcitonin from patients with sepsis

Cited by 59 publications

References 14 publications

Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators

Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators

Method for the Selective Measurement of Amino-Terminal Variants of Procalcitonin

Neutrophil/lymphocyte ratio: A promising prognostic marker in patients with chronic kidney disease

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