calca-protein--human and Lupus-Erythematosus--Systemic

Early differentiation between infection and aseptic inflammation is difficult and is a challenge often faced in the rheumatology practice. Procalcitonin (PCT) is a biomarker that is preferentially induced in patients with bacterial infections, and a growing body of evidence supports its use for improving diagnosis of bacterial infections and guiding antibiotic therapy. In this article, we review the evidence for the use of PCT measurement in rheumatology practice. Several studies have examined the use of PCT to assist in the differentiation between septic and non-septic arthritis in patients with an inflamed joint and found it to be a sensitive and specific marker of infection. A number of studies in patients with diverse inflammatory rheumatic diseases have provided useful information regarding the usefulness of PCT in these patients. In summary, PCT when used in the appropriate clinical setting can be a useful adjunct to currently available laboratory infection markers, though further studies are warranted. Furthermore, PCT results should be interpreted in parallel with the clinical assessment.

Topics: Anti-Bacterial Agents; Arthritis; Arthritis, Infectious; Arthritis, Rheumatoid; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Early Diagnosis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Prosthesis-Related Infections; Protein Precursors; Still's Disease, Adult-Onset; Systemic Vasculitis

Distinction between infection and febrile disease flare in patients with systemic lupus erythematosus (SLE) is fundamental but often difficult to make, because clinical presentation can be similar. A systematic review of all articles indexed in PubMed through October 2013 was performed, in order to examine the potential role of procalcitonin (PCT) for the discrimination between SLE flare and infection. Among the 12 papers identified, 5 articles reported on PCT levels in SLE patients without infection, 6 compared PCT levels between SLE patients with flare versus those with infection, and 1 analyzed PCT levels in active patients with and without bacterial infection. These data suggest the absence of correlation between PCT levels and SLE disease activity. Furthermore, PCT levels detected during disease flares are lower than those observed during bacterial infections. PCT can therefore be used accurately in the early differentiation between bacterial infection and flare in febrile SLE patients. Raised PCT levels ≥0.5 μg/L should strongly suggest bacterial infection in the context of SLE, keeping in mind the limited data available in case of hemophagocytic syndrome. Elevated PCT levels in SLE patients should always prompt a thorough search for sources of potential infection.

Topics: Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Lupus Erythematosus, Systemic; Protein Precursors

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.. 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.. 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.. 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.

Topics: Anti-Glomerular Basement Membrane Disease; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Arthritis, Rheumatoid; Autoimmune Diseases; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Giant Cell Arteritis; Humans; Lupus Erythematosus, Systemic; Predictive Value of Tests; Protein Precursors

Data on the origin and biological function of procalcitonin, the pro-hormone of calcitonin, are scarce. Since this peptide can be induced in bacterial invasive infections, serum procalcitonin levels may be useful in differential diagnosis of systemic inflammatory response syndrome. This review will focus on the clinical significance of changes in serum procalcitonin levels in patients with connective tissue diseases and other rheumatic disorders.

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Connective Tissue Diseases; Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Lupus Erythematosus, Systemic; Mycoses; Protein Precursors; Rheumatic Diseases; Virus Diseases

To study the clinical value of procalcitonin (PCT) and C-reactive protein (CRP) in differentiating bacterial infection from disease activity in systemic lupus erythematosus (SLE) patients.. PCT and CRP in active SLE patients complicated with and without bacterial infection were retrospectively studied. Bacterial infection was diagnosed by positive culture results or typical symptoms and signs combined with positive response to antibiotics. Disease activity of SLE was assessed by systemic lupus erythematosus disease activity index (SLEDAI).. One hundred and fourteen active SLE patients were recruited, 47 of which were with bacterial infection and 67 were non-infected. PCT and CRP levels were significantly elevated in patients with bacterial infection (P < 0.05). The ideal cutoff value for PCT was 0.38 ng/ml, at which the sensitivity (74.5%) and specificity (95.5%) combined the best. The negative predictive value and positive predictive value to detect bacterial infection were 84.2% and 92.1%, respectively. PCT but not the CRP level in the septic patients was significantly higher than that of non-septic ones. Meanwhile, in patients with SLEDAI score of > 10, both PCT and CRP levels were higher in patients with bacterial infection, but the difference was only statistically significant for PCT (P < 0.05). PCT was significantly reduced after anti-bacterial treatment.. PCT test is superior to CRP test in detecting superimposed bacterial infection in active SLE patients. The levels of PCT are correlated with the severity of bacterial infection and can be used to monitor the response to antibiotic treatment.

Topics: Adolescent; Adult; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Young Adult

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Lupus Erythematosus, Systemic; Protein Precursors

C-reactive protein (CRP), S100A8/A9, and procalcitonin have been suggested as markers of infection in patients with systemic lupus erythematosus (SLE). We investigated the clinical significance of these factors for indication of infection in SLE.. Blood samples were prospectively collected from 34 patients with SLE who had bacterial infections and 39 patients with SLE who had disease flares and no evidence of infection. A second set of serum samples was collected after the infections or flares were resolved.. CRP levels of SLE patients with infections were higher than those with flares [5.9 mg/dl (IQR 2.42, 10.53) vs 0.06 mg/dl (IQR 0.03, 0.15), p < 0.001] and decreased after the infection was resolved. S100A8/A9 and procalcitonin levels of SLE patients with infection were also higher [4.69 μg/ml (IQR 2.25, 12.07) vs 1.07 (IQR 0.49, 3.05) (p < 0.001) and 0 ng/ml (IQR 0-0.38) vs 0 (0-0) (p < 0.001), respectively]; these levels were also reduced once the infection disappeared. In the receiver-operating characteristics analysis of CRP, S100A8/A9, and procalcitonin, the area under the curve was 0.966 (95% CI 0.925-1.007), 0.732 (95% CI 0.61-0.854), and 0.667 (95% CI 0.534-0.799), respectively. CRP indicated the presence of an infection with a sensitivity of 100% and a specificity of 90%, with a cutoff value of 1.35 mg/dl.. Our data suggest that CRP is the most sensitive and specific marker for diagnosing bacterial infections in SLE.

Topics: Adult; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Calgranulin A; Calgranulin B; Female; Humans; Lupus Erythematosus, Systemic; Male; Opportunistic Infections; Predictive Value of Tests; Protein Precursors; Young Adult

Previous studies in systemic lupus erythematosus (SLE) patients have produced conflicting results regarding the diagnostic utility of procalcitonin (PCT). The aim of this study was to determine predictive values of PCT and C-reactive protein (CRP) for bacterial infection in SLE patients.. This was a cross-sectional study of clinic and hospitalized SLE patients with and without bacterial infection recruited over 18 months. Bacterial infection was defined as positive culture results. SLE disease activity was measured using SLEDAI. PCT and CRP were measured by automated immunoassays.. Sixty-eight patients (57 females) were studied. Ten patients (15%) had infection. The areas under the receiver operating characteristic curves for PCT and CRP were not significantly different [0.797 (CI 0.614-0.979) versus 0.755 (CI 0.600-0.910)]. In lupus flare patients, PCT but not CRP was higher with infection (p = 0.019 versus 0.195). A PCT of <0.17 ng/ml ruled out infection with 94% negative predictive value (NPV). In remission patients, CRP but not PCT was elevated with infection (p = 0.036 versus 0.103). CRP < 0.57 mg/dl had 96% NPV.. PCT may be a better marker to rule out bacterial infection in lupus flare but not in remission or general screening.

Topics: Adolescent; Adult; Automation; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross-Sectional Studies; Female; Humans; Immunoassay; Lupus Erythematosus, Systemic; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; ROC Curve; Severity of Illness Index; Young Adult

Systemic erythematosus lupus (SLE) is a common autoimmune disease. Disease flares may mimic infection with fever, inflammatory syndrome and chills, sometimes resulting in a difficult differential diagnosis. Elevated serum procalcitonin (PCT) levels have been reported to be predictive of bacterial infections, but with conflicting results. The value of serum procalcitonin has not been assessed in large series of SLE. We aimed to describe the distribution of PCT levels in SLE patients with and without flares, to assess the factors associated with increased PCT levels, and to determine the positive and negative predictive values of increased PCT for bacterial infection in SLE patients. Hospitalized SLE patients were included in a retrospective study. Serum PCT had been assayed, or a serum sample had been frozen on admission, before treatment modification. Serum PCT, measured by an automated immunofluorometric assay, and SLEDAI were assessed at the same time. Some 53 women (median age: 33.7 years, range 16-76) and seven men (median age: 52.5 years ± 19) were included. The median SLEDAI for patients with flare (n = 16, 28%) was 2 (range: 0-29). Five patients (8%) had systemic infection. Only one patient had increased PCT levels. Men had significantly higher PCT levels than women (0.196 ± 0.23 versus 0.066 ± 0.03, p < 0.01) and a significant correlation was observed between PCT, age, erythrocyte sedimentation rate, and C-reactive protein. We conclude that PCT levels were within the normal range in infected and non-infected SLE patients and there was no ability to differentiate SLE patients with or without bacterial infection.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Disease Progression; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sex Factors; Young Adult

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by tissue injury mediated by inflammatory mechanisms. Nonetheless, several acute-phase proteins may remain normal or are decreased. We explore the association of diverse biomarkers with selected clinical features, disease activity, and organ damage in SLE.. One hundred and fifteen SLE patients were analyzed for clinical manifestations, disease activity, and organ damage. Serum C-reactive protein (CRP), complement C3, C4 and CH50%, alpha-1-antitrypsin (AAT), transferrin (Tf), procalcitonin, erythrosedimentation rate (ESR), and interleukin-6 were measured in patients and twenty-six healthy blood donors. Statistics include chi-square, Kruskal-Wallis (post hoc by Mann-Whitney) or one-way ANOVA tests (post hoc by t tests) as appropriate. Associations were evaluated by the Spearman's correlation coefficient (p).. SLE patients have lower C3 (85 vs. 110 mg/dL; p < 0.0001) and C4 (14.2 vs. 24.2 mg/dL; p < 0.0001) than controls, while CRP (4.1 vs. 1.4 mg/L; p = 0.005) and AAT (147 vs. 138 mg/dL; p = 0.03) were higher, other biomarkers were irrelevant. Disease activity score positively correlated with ESR (p = 0.23, 95 % CI 0.04 to 0.4; p = 0.01) and CRP (p = 0.19, 0.0007 to 0.36; p = 0.04), while inverse correlations with C3 (p = -0.26, -0.43 to -0.08; p = 0.004), C4 (p = -0.18, -0.36 to 0.005; p = 0.04), CH50 % (p = -0.20, -0.38 to -0.01; p = 0.02), and Tf (p = -0.35, -0.53 to -0.12; p = 0.002) were found. According to clinical manifestations, patients with arthritis showed higher levels of ESR (34 vs. 20 mm/h), CRP (10 vs. 2.8 mg/L), and AAT (179 vs. 145 mg/dL), but lower Tf (192 vs. 226 mg/dL) than those without arthritis; whereas active nephritis was characterized by lower serum concentrations of complement C3 (73 vs. 92 mg/dL), C4 (10 vs. 15 mg/dL), CH50% (80 vs. 160 U/mL) and Tf (196 vs. 232 mg/dL) than those patients without this manifestation. No other significant differences were found.. In patients with SLE, acute-phase proteins behave differently depending on the kind of organ damage evaluated. Serum complement proteins remained as the most reliable laboratory markers for nephritis, while CRP was determined the best in patients with arthritis. The muted CRP response seen in SLE patients with active nephritis could have important pathogenic implications.

Topics: Acute-Phase Proteins; Adult; alpha 1-Antitrypsin; Antimalarials; Antirheumatic Agents; Arthritis; Biomarkers; Blood Sedimentation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Complement System Proteins; Cross-Sectional Studies; Exanthema; Female; Humans; Immunosuppressive Agents; Interleukin-6; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Mental Disorders; Middle Aged; Organ Specificity; Protein Precursors; Transferrin; Vasculitis; Young Adult

Procalcitonin (PCT), the precursor of the calcitonin, is synthesized in the parafollicular C-cells of the thyroid. It has been used to detect and to differentiate systemic bacterial infections from flares of systemic lupus erythematosus (SLE). PCT in serum increases in severe bacterial and fungal infections, but not, or only slightly in viral infections.. To measure PCT levels in patients with active SLE and to compare them with patients without lupus activity and to determine the possible association between activity and elevation of the PCT.. Prospective case control study.. Measurements were made of PCT (METHOD: Essay immunoluminometric--and ultrasensitive--BRAHMS Diagnostika, Berlin, Germany), C-reactive protein, erythrocyte sedimentation rate, and blood and urine cultures. The index of activity of SLE was determined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of a serial group of patients seen by our rheumatology service. Samples from 53 patients were analyzed. The patients were divided in 2 groups: group I (n = 21) with little or no activity for SLE; group II (n = 32) with activity for SLE (SLEDAI >5). None of the patients had severe bacterial infection, sepsis, or systemic multiorgan failure.. Group I had a SLEDAI score of 1.8 [95% confidence interval (CI) 1.09-2.51] with mean levels of PCT 0. 08 ng/mL (Negative smaller than 0. 5 ng/mL). Group II SLEDAI score was 14.6 (95% CI 11.95-17.23) with mean levels of PCT 0.418 ng/mL with standard deviation 1.0021 (95% CI 0.0628-0.773). The measure of association calculated by Fisher method was not significant (1.927) (P = 0. 282). In the group II, 3 patients had frankly positive PCT (3.18, 3.42, and 3.95 ng/mL) and high activity indices (14, 13, and 24). None presented with severe infection, sepsis, or systemic multiorgan failure. They had pneumonia, renal failure (PCT 3.42 ng/mL) and urinary tract infection without systemic symptoms (3.95 ng/mL). Infection was not detected in the other patient (3.18 ng/mL) that was interpreted as a false positive.. This study demonstrates that there is no association between the activity of SLE and PCT levels. The utility of the PCT resides is in raising suspicion of a concurrent bacterial or mycotic infection in the evaluation of patients with active autoimmune diseases.

Topics: Adult; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Lupus Erythematosus, Systemic; Male; Mycoses; Prospective Studies; Protein Precursors; Severity of Illness Index

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Lupus Erythematosus, Systemic; Prospective Studies; Protein Precursors

To investigate whether serum procalcitonin (PCT) levels could be useful to differentiate between systemic infection and the activity of the underlying disease in autoimmune disease.. In 18 patients with systemic lupus erythematodes (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV) clinical disease activity was assessed by score systems. Infection was defined by clinical and microbiological means. PCT was determined in parallel with concentrations of neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP) in 397 serum samples.. Only in 3 of the 324 samples taken from patients with autoimmune disease but without concomitant infection, serum PCT levels were above the normal range (>0.5 ng/ml), whereas neopterin, CRP and IL-6 were elevated in patients with active underlying disease. All systemic infections (N=16 in AAV-patients) were associated with markedly elevated PCT-levels (mean+/-SD:1.93+/-1.19 ng/ml).. PCT may serve as a useful marker for the detection of systemic bacterial infection in patients with autoimmune disease.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Protein Precursors; Sensitivity and Specificity; Vasculitis

Topics: Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Lupus Erythematosus, Systemic; Protein Precursors; Vasculitis

To investigate whether the determination of serum procalcitonin (PCT) in systemic autoimmune disease will help to discriminate invasive infection from highly active underlying disease.. Three hundred ninety-seven serum samples, from 18 patients with systemic lupus erythematosus (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV), were analyzed. Clinical disease activity was assessed by the Systemic Lupus Activity Measure in SLE patients and by the Birmingham Vasculitis Activity Score in AAV patients. Procalcitonin concentrations were determined in parallel with concentrations of neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP). Additionally, serum creatinine values were obtained.. In 321 of the 324 samples from the 42 patients with autoimmune disease but without systemic infection, serum PCT levels were within the normal range (i.e., <0.5 ng/ml), whereas the values for neopterin, IL-6, and CRP were elevated in patients with active underlying disease. All 16 systemic infections occurred in 11 patients with AAV, and were associated with PCT levels that were markedly elevated, to a mean +/- SD of 1.93 +/- 1.19 ng/ml. No correlation between the degree of renal impairment and PCT concentrations was seen.. PCT may serve as a useful marker for the detection of systemic bacterial infection in patients with systemic autoimmune disease.

Topics: Antibodies, Antineutrophil Cytoplasmic; Autoimmune Diseases; Bacterial Infections; Biomarkers; Biopterins; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Diagnosis, Differential; Glycoproteins; Granulomatosis with Polyangiitis; Humans; Interleukin-6; Lupus Erythematosus, Systemic; Neopterin; Protein Precursors; Vasculitis