Procalcitonin
Serum Procalcitonin in Systemic Autoimmune Diseases—Where Are We Now?

https://doi.org/10.1016/j.semarthrit.2009.10.004Get rights and content

Objectives

To review the current evidence regarding the value of measuring procalcitonin (PCT) levels in patients with systemic autoimmune diseases, with a focus on the evidence for diagnostic and analytical performance of this biomarker. A brief description of the pathophysiological basis of this biomarker is also included.

Methods

Using PubMed from the National Library of Medicine, relevant English literature on PCT in patients with different systemic autoimmune diseases, from 1990 to 2009, was reviewed. The search used keywords referring to procalcitonin and systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated systemic vasculitis, Goodpasture syndrome, rheumatoid arthritis, and giant cell arteritis.

Results

When used in the appropriate clinical setting, the measurement of serum PCT levels is valuable as a marker of severe systemic bacterial and fungal infections and sepsis. Information regarding plasma PCT levels in patients with active underlying systemic autoimmune diseases is limited, primarily from observational studies and case series, with considerable variability of patient characteristics and clinical settings. In the detection of systemic infection concomitant with autoimmune diseases, PCT had a diagnostic sensitivity of 53 to 100% and a specificity of 84 to 97% (depending on the selection criteria) and was superior to other inflammatory markers tested. Most of the studies used a semiquantitative test for PCT measurement (functional assay sensitivity <0.5 ng/mL), which can explain the low sensitivity of the test. PCT levels were not significantly affected by renal function abnormalities or immunosuppressive agents. Although high PCT levels commonly occurred with infection, elevated levels of PCT could be found in patients with vasculitis without evidence of infection, often correlated with high disease activity scores.

Conclusions

Significantly elevated PCT levels offer good specificity and sensitivity for systemic infection in patients with systemic autoimmune diseases, regardless of the use of corticosteroids or immunosuppressive agents. PCT measurement may add to diagnostic accuracy in patients with systemic autoimmune diseases who present with a febrile illness, especially when highly sensitive PCT assays and specific PCT cutoff ranges are used in a predefined clinical setting (reflecting the likelihood of infection versus an autoimmune disease flare). However, there are limitations when using this biomarker in patients with systemic autoimmune diseases. PCT levels should not replace the necessary extensive diagnostic workup, which should include a thorough history and physical examination, combined with appropriate immunological, microbiological, radiological, and histological data.

Section snippets

Methods

Here we review the current evidence regarding the value of measuring PCT levels in patients with systemic autoimmune diseases, with focus on the evidence for diagnostic and analytical performance of this biomarker. Using PubMed from the National Library of Medicine, relevant English literature on PCT levels in patients with different systemic autoimmune diseases, from 1990 to 2009, was reviewed. The search included the keywords procalcitonin, systemic lupus erythematosus (SLE), antineutrophil

Pathophysiology of Procalcitonin in Systemic Infection

PCT, a 116-amino-acid protein with a molecular weight of 13 KDa, is the precursor in the synthesis of calcitonin (CT), a calcium-regulating peptide with a role in calcium homeostasis. CT production results from transcription of the CALC-I gene, which, in a normal individual, is restricted to neuro-endocine cells, mainly C cells of the thyroid. However, it has been demonstrated that after thyroidectomy there is increased PCT release in severe inflammatory states, suggesting that the site of PCT

Discussion

Recognizing the strengths and weaknesses of measuring of PCT levels is important for accurate and safe use in clinical practice. An important drawback of the published evidence on PCT in systemic autoimmune diseases is the lack of true outcome studies, where clinical decisions are guided by a PCT algorithm, as implemented in respiratory tract infections (50) and sepsis (51). Furthermore, most of the published observational studies on PCT in autoimmune diseases used a semiquantitative test for

References (54)

  • M.S. Rangel-Frausto et al.

    The natural history of the systemic inflammatory response syndrome (SIRS)A prospective study

    J Am Med Assoc

    (1995)
  • B. Muller et al.

    High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration

    J Leukoc Biol

    (2002)
  • T. Nishikura

    Procalcitonin (PCT) production in a thyroidectomized patient

    Intensive Care Med

    (1999)
  • B. Müller et al.

    Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis

    J Clin Endocrinol Metab

    (2001)
  • K.L. Becker et al.

    Clinical review 167: procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors

    J Clin Endocrinol Metab

    (2004)
  • K.T. Whang et al.

    Procalcitonin and proinflammatory cytokine interactions in sepsis

    Shock

    (2000)
  • G. Hoffmann et al.

    Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells

    Crit Care Med

    (2002)
  • E.S. Nylen et al.

    Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis

    Crit Care Med

    (1998)
  • H.L. Preas et al.

    Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia

    J Infect Dis

    (2001)
  • W. Karzai et al.

    Procalcitonin—a new indicator of the systemic response to severe infections

    Infection

    (1997)
  • D. Gendrel et al.

    Procalcitonin—a marker of bacterial infection

    Infection

    (1997)
  • B. Müller et al.

    Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit

    Crit Care Med

    (2000)
  • S. Schwarz et al.

    Serum procalcitonin levels in bacterial and abacterial meningitis

    Crit Care Med

    (2000)
  • B.M. Rau et al.

    Early assessment of pancreatic infections and overall prognosis in severe acute pancreatitis by procalcitonin (PCT): a prospective international multicenter study

    Ann Surg

    (2007)
  • B.J. Ammori et al.

    Calcitonin precursors: early markers of gut barrier dysfunction in patients with acute pancreatitis

    Pancreas

    (2003)
  • M.L. Kylänpää-Bäck et al.

    Procalcitonin strip test in the early detection of severe acute pancreatitis

    Br J Surg

    (2001)
  • D. Gendrel et al.

    Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections

    Pediatr Infect Dis J

    (1999)
  • Cited by (58)

    • Markedly elevated procalcitonin due to anaphylactic shock, a case report

      2022, Heliyon
      Citation Excerpt :

      PCT of mild elevated levels between 0.15 and 2 ng/mL usually indicates localized mild to moderate bacterial infection, noninfectious systemic inflammation, or untreated end-stage kidney disease [3]. It also can be found to be elevated in trauma and autoimmune disease patients [4, 5]. High levels of PCT of more than 2 ng/mL are associated with bacterial sepsis, severe localized bacterial infection, or medullary thyroid carcinoma [3].

    • Diagnostic and predictive values of procalcitonin in bloodstream infections for nosocomial pneumonia

      2018, Journal of Critical Care
      Citation Excerpt :

      PCT levels can be affected by some non-infectious diseases, such as autoimmune diseases [12-16] and malignant tumors [17-19]. Therefore, the exclusion criteria were: [1] a medical history of immune system disease (adult-onset Still's disease, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, vasculitis, or multiple sclerosis) [12-16]; and [2] a history of malignant tumor (thyroid carcinoma or lung cancer) [17-19]. Serum PCT levels were measured using an automatic analyzer (Vidas B.R.A.H.M.S.; bioMérieux, Marcy l'Etoile, France), according to the manufacturer's instructions.

    • Infections and Paraproteinemia

      2022, Paraproteinemia and Related Disorders
    View all citing articles on Scopus
    View full text