Serum Pancreatic Stone Protein Research Articles

Role of Serum Pancreatic Stone Protein as a New Biomarker for Diagnosis of Late Onset Neonatal Sepsis

Role of Serum Pancreatic Stone Protein as a New Biomarker for Diagnosis of Late Onset Neonatal Sepsis

The Role of Pancreatic Stone Protein (PSP) as a Biomarker of Pregnancy-Related Diseases.

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions.

Serum Pancreatic Stone Protein Reference Values in Healthy Pregnant Women: A Prospective Cohort Study.

In non-pregnant populations, pancreatic stone protein (PSP) has been reported to have a higher diagnostic performance for identifying severe inflammatory and infectious disease than other established biomarkers. To generate reference values for serum PSP in pregnancy and compare them to the values of the general healthy population. A prospective cohort study. A single center. Healthy women with singleton and multiple pregnancies. This is a prospective single-center cohort study. Between 2013 and 2021, samples of 5 mL peripheral blood were drawn from 440 healthy pregnant women. Therein, 393 cases were singletons and 47 were multiple pregnancies. Serum PSP levels were measured by specific enzyme-linked immunosorbent assay. The main outcome measures were serum PSP level (ng/mL) reference values in healthy pregnant women. The mean PSP reference values in women with singleton pregnancies were 7.9 ± 2.6 ng/mL (95% CI; 2.69-13.03 ng/mL). The PSP values in women with multiple pregnancies (9.17 ± 3.06 ng/mL (95% CI; 3.05-15.28 ng/mL)) were significantly higher (p = 0.001). The PSP values in the first trimester (6.94 ± 2.53 ng/mL) were lower compared to the second (7.42 ± 2.21 ng/mL) and third trimesters (8.33 ± 2.68 ng/mL, p = 0.0001). Subgroup analyses in singletons revealed no correlations between PSP values, maternal characteristics, and pre-existing medical conditions. The PSP values in healthy pregnant women (4-12 ng/mL) were in the range of the reference values of the general healthy population (8-16 ng/mL). This insight blazes a trail for further clinical studies on the use of PSP as a potential novel biomarker for the early detection of pregnancy-related diseases such as chorioamnionitis.

Pediatric sepsis diagnostic and prognostic biomarkers: pancreatic stone protein, copeptin, and apolipoprotein A-V

BackgroundWe assessed serum concentrations of pancreatic stone protein (PSP), copeptin, and apolipoprotein A-V (APOA5) biomarkers for the diagnosis and prognosis of pediatric sepsis, a condition associated with high mortality.MethodsThis prospective study included 180 children admitted to the Pediatric Intensive Care Unit and 100 healthy controls at Menoufia University Hospital. Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality-2 (PIM2), and Pediatric Sequential Organ Failure Assessment (pSOFA) scores were calculated. Serum PSP, copeptin and APOA5 were measured once within 24 h of admission.ResultsPSP, copeptin, and APOA5 were significantly higher in the patients than in the controls (p < 0.001). PSP and copeptin were increased among children who required mechanical ventilation (MV), had multiple organ dysfunctions, and were non-survivors, but APOA5 was decreased in those children. Logistic regression analyses showed that high pSOFA, high PSP and copeptin, low APOA5, and use of MV were associated with mortality. The receiver operating characteristic revealed that the area under the curve (AUC) for APOA5, copeptin, and PSP (0.965, 0.960, and 0.868, respectively) demonstrated high sensitivity (96%, 94%, and 80%) for sepsis diagnosis. The AUC values for PSP, copeptin, and APOA5 were 0.709, 0.705, and 0.571, respectively, with sensitivities of 74%, 58%, and 58% for mortality prediction.ConclusionsPSP, copeptin, and APOA5 are promising diagnostic biomarkers for pediatric sepsis but inadequate predictors of mortality.ImpactApolipoprotein A-V (APOA5), copeptin, and pancreatic stone protein (PSP) are acute-phase proteins with diagnostic value in evaluating critically ill pediatric patients with sepsis and detecting sepsis severity.PSP and copeptin had the power to discriminate non-survivors from survivors.APOA5 was less powerful than the other biomarkers in discriminating between survivors and non-survivors.

Serum Pancreatic Stone Protein as a New Protein Biomarker for Late-onset Neonatal Sepsis

Background: Neonatal sepsis is an important cause of neonatal morbidity and mortality worldwide. Early diagnosis is the cornerstone of management and favorable outcome. The wide variations of presenting signs of neonatal sepsis make reaching a diagnosis very challenging.Objectives: Our aim was to study serum pancreatic stone protein (PSP) in late-onset neonatal sepsis and its relation to the clinical score and C-reactive protein (CRP).Results: We found that the definite sepsis group had significantly higher PSP and CRP levels than the other two groups (p < 0.001). Moreover, the probable sepsis group had significantly higher PSP and CRP levels than controls (p < 0.001). The PSP had significant positive correlations with the clinical score (r=0.32, P =0.01) and CRP level (r=0.47, P =0.001). The PSP was more sensitive than both clinical score and CRP in detecting neonatal sepsis, as its sensitivity was 98.3% and a specificity of 100%.Conclusion: PSP is a valuable biomarker to detect late-onset neonatal sepsis. It is more sensitive than traditionally used acute phase reactant as CRP.

The value of pancreatic stone protein in the prediction of infected neonates.

The aim of this study was to determine serum pancreatic stone protein (PSP) levels in the neonates with highly probable or probable sepsis and assess their possible value in predicting infected neonates. This was a prospective study involving 119 neonates who were admitted with suspected sepsis. The study population was divided into two groups, a infected group (N.=40, with highly probable sepsis or probable sepsis) and control group (N.=79, with possible or no sepsis). The blood samples were obtained at 24, 72 and 168 hours after birth. The amount of serum PSP were detected by enzyme linked immunosorbent (ELISA). PSP serum concentrations were higher in the infected group comparison to the control group at all time points (all P=0.000). In addition the sequential comparison between the infected group and control group at all of time points was significantly different (F=48.558, P=0.000). ROC area under the curve (AUC) was 0.791 [95% CI: 0.71-0.87; P=0.000] for PSP at 24 hours after birth and 0.790 (95% CI: 0.79-0.88; P=0.000) 72 hours after birth and combination of the two time points (24 and 72 hours), the AUC was 0.819 (95% CI: 0.74-0.90; P=0.000). PSP is a valuable biomarker in predicting infected neonates. Combination of PSP at each time point within 72 hours after birth might be better.

The Role of Pancreatic Stone Protein in Diagnosis of Early Onset Neonatal Sepsis

Introduction. Early diagnosis and treatment of neonatal sepsis may help decrease neonatal mortality. Aim of the Study. To evaluate the role of pancreatic stone protein as a marker for early onset neonatal sepsis. Methods. A hospital-based prospective study was conducted on 104 (52 uninfected and 52 infected neonates) admitted to the Neonatal Intensive Care Unit (NICU) of Zagazig University hospitals during the period from April 2014 to April 2015. All newborns were subjected to full history taking, careful neonatal assessment, blood, C-reactive protein (CRP), and serum pancreatic stone protein. Results. Serum PSP levels were significantly higher in the infected group than in the uninfected group. At a cutoff level of PSP 12.96 ng/mL, the sensitivity was 96.2%, the specificity was 88.5%, positive predictive value was 95.8%, negative predictive value was 89.3%, and area under the curve was 0.87. A significant positive correlation between CRP and PSP was found in infected group. Conclusion. The high negative predictive value of PSP (89.3%) indicates that the serum PSP level is a good marker for diagnosis of early onset neonatal sepsis and can be used to limit hospital stay and antibiotic use in neonates treated for suspected sepsis.

Pancreatic stone protein predicts postoperative infection in cardiac surgery patients irrespective of cardiopulmonary bypass or surgical technique.

IntroductionWe investigated the role of pancreatic stone protein (PSP) in predicting the occurrence of infection in the postoperative course of cardiac surgery patients. Several biomarkers indicating the presence of inflammation and infection are available in the clinical routine; yet, their utility in the postoperative course of patients following cardiac surgery remains uncertain. Moreover, cardiopulmonary bypass, also referred to as “on-pump surgery”, increases the susceptibility to an exaggerated inflammatory state. However, the impact of such extracorporeal circulation on circulating PSP levels remains poorly understood.MethodsIn a prospective cohort of unselected patients undergoing cardiac surgery, we set out to elucidate the diagnostic accuracy of serum PSP levels as opposed to canonical biomarkers (CRP, WBC) of inflammation to discriminate between the presence of infection and surgical trauma,. In addition, we investigated whether the biomarkers were influenced by the surgical technique employed, i.e. on-pump vs. off-pump and minimally invasive surgery vs. sternotomy. Levels of circulating PSP and routine inflammatory biomarkers (CRP, WBC) were measured in samples taken from 120 patients at baseline as well as at postoperative day 1–3.ResultsUnivariate analysis showed that among the biomarkers investigated, only PSP levels had discriminatory power to differentiate infection from surgical trauma in the postoperative course of the entire cohort of patients following cardiac surgery. With regard to cardiac surgical interventions, there was no significant association between the absence or presence of extracorporeal circulation and PSP levels. However, there was a significant difference in the slope of the rise of postoperative PSP between minimally invasive surgery as opposed to patients subjected to sternotomy.ConclusionIn an unselected population of cardiac surgery patients, post-operative serum PSP levels were significantly associated with the presence of infection in both the on-pump and off-pump setting. Of note, the surgical technique employed (sternotomy vs. minimally invasive approach) had a significant impact on postoperative PSP levels.

Effects of hepatocyte nuclear factor-1A and -4A on pancreatic stone protein/regenerating protein and C-reactive protein gene expression: implications for maturity-onset diabetes of the young

BackgroundThere is a significant clinical overlap between patients with hepatocyte nuclear factor (HNF)-1A and HNF4A maturity-onset diabetes of the young (MODY), two forms of monogenic diabetes. HNF1A and HNF4A are transcription factors that control common and partly overlapping sets of target genes. We have previously shown that elevated serum pancreatic stone protein / regenerating protein A (PSP/reg1A) levels can be detected in subjects with HNF1A-MODY. In this study, we investigated whether PSP/reg is differentially regulated by HNF1A and HNF4A.MethodsQuantitative real-time PCR (qPCR) and Western blotting were used to validate gene and protein expression in cellular models of HNF1A- and HNF4A-MODY. Serum PSP/reg1A levels and high-sensitivity C-reactive protein (hsCRP) were measured by ELISA in 31 HNF1A- and 9 HNF4A-MODY subjects. The two groups were matched for age, body mass index, diabetes duration, blood pressure, lipid profile and aspirin and statin use.ResultsInducible repression of HNF1A and HNF4A function in INS-1 cells suggested that PSP/reg induction required HNF4A, but not HNF1A. In contrast, crp gene expression was significantly reduced by repression of HNF1A, but not HNF4A function. PSP/reg levels were significantly lower in HNF4A subjects when compared to HNF1A subjects [9.25 (7.85-12.85) ng/ml vs. 12.5 (10.61-17.87) ng/ml, U-test P = 0.025]. hsCRP levels were significantly lower in HNF1A-MODY [0.22 (0.17-0.35) mg/L] compared to HNF4A-MODY group [0.81 (0.38-1.41) mg/L, U-test P = 0.002], Parallel measurements of serum PSP/reg1A and hsCRP levels were able to discriminate HNF1A- and HNF4A-MODY subjects.ConclusionOur study demonstrates that two distinct target genes, PSP/reg and crp, are differentially regulated by HNF1A and HNF4A, and provides clinical proof-of-concept that serum PSP/reg1A and hsCRP levels may distinguish HNF1A-MODY from HNF4A-MODY subjects.

Pancreatic Stone Protein Predicts Outcome in Patients With Peritonitis in the ICU*

To determine the value of pancreatic stone protein in predicting sepsis-related postoperative complications and death in the ICU. A prospective cohort study of postoperative patients admitted to the ICU. Blood samples for analysis were taken within 3 hours from admission to the ICU including pancreatic stone protein, white blood cell counts, C-reactive protein, interleukin-6, and procalcitonin. The Mannheim Peritonitis Index and Acute Physiology and Chronic Health Evaluation II clinical scores were also determined. Univariate and multivariate analyses were performed to determine the diagnostic accuracy and independent predictors of death in the ICU [Clinicaltrials.gov, NCT01465711]. An adult medical-surgical ICU in a teaching hospital in Germany. Ninety-one consecutive postoperative patients with proven diagnosis of secondary peritonitis admitted to the ICU were included in the study from August 17, 2007, to February 8, 2010. Peripheral vein blood sampling. Univariate analysis demonstrated that pancreatic stone protein has the highest diagnostic accuracy for complications and is the best predictor for death in the ICU. Pancreatic stone protein had the highest overall efficacy in predicting death with an odds ratio of 4.0 vs. procalcitonin (odds ratio 3.2), interleukin-6 (odds ratio 2.8), C-reactive protein (odds ratio 1.3), and WBCs (odds ratio 1.4). By multivariate analysis, pancreatic stone protein was the only independent predictor of death. In a population of patients with sepsis-related complications, serum-pancreatic stone protein levels demonstrate a high diagnostic accuracy to discriminate the severity of peritonitis and to predict death in the ICU. This test could be of value in the clinical diagnosis and therapeutic decision making in the ICU.

Molecular forms of serum pancreatic stone protein in acute pancreatitis.

Elevation of serum pancreatic stone protein-(PSP) S1 suggests activation of trypsinogen in the pancreas. This information would prompt the start of intensive treatment and may improve prognosis of acute pancreatitis (AP). PSP exists in two molecular forms, PSP-S2-5 and PSP-S1. PSP-S1 is produced by enzyme cleavage of PSP-S2-5 by trypsin. Total serum PSP rose in AP, but little is known about its molecular forms. In this study, we characterized the molecular forms of serum PSP in AP. Sera were taken from 8 patients with severe acute pancreatitis (sAP) and from 11 patients with mild acute pancreatitis (mAP). Serum PSP was characterized by high-performance liquid chromatography (HPLC) followed by the specific enzyme immunoassay (EIA). The total serum PSP in sAP was higher than in mAP, but the difference was not significant. The PSP-S1 was detected in serum in all (7/7) patients in sAP and in 72% (8/11) of patients in mAP. Serum level of PSP-S1 was significantly higher in sAP than that in mAP (p < 0.05), and the cutoff value to distinguish the two groups was 30 ng/mL. Serum PSP-S1 did not show significant correlation with total PSP, immunoreactive trypsin, or C-reactive protein.

Serum pancreatic stone protein in pancreatic diseases.

Serum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean +/- SD = 1075.4 +/- 2849.1 ng/mL, n = 33) was significantly higher than that in controls (78.6 +/- 31.8 ng/mL, n = 37, p < 0.01), chronic pancreatitis (156.8 +/- 82.8 ng/mL, n = 32, p < 0.05), and pancreatic cancer (148.468.8 ng/mL, n = 26, p < 0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0 +/- 1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r = 0.22, p < 0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflex from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis.

Enzyme immunoassay and immunochemical characterization of pancreatic stone protein in human serum.

Monoclonal antibodies were raised against human pancreatic stone protein (PSP) and used for one-step enzyme immunoassay (EIA). PSP-S2-5 was employed as the standard in the assay. The assay's measurable range was 25-1,500 ng/ml and within run coefficient of variation was 3.7-6.4%. Analytical recovery of the assay was 101.5 +/- 5.65% (mean +/- SD). The results of experiments in which serum was fractionated by Mono S (cation exchange chromatography) suggested that most of immunoreactive material in human serum is PSP-S2-5. The EIA offers simple, rapid, and specific analysis of serum PSP level for clinical diagnosis.

Immunochemical characterization and quantitative distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders

A fluorometric immunoassay has been established to quantitate pancreatic stone protein providing a sensitivity for concentrations from 0.015 to 0.5 μg/mL. When concentrations of pancreatic stone protein were determined from pancreatic secretions obtained either from patients suffering from chronic pancreatitis (n = 31) [including the calcifying forms (n = 10)], pancreatic cancer (n = 22), or nonpancreatic diseases (n = 17), no significant differences were found. In contrast, increased concentrations were found in serum samples from patients with chronic (39/66) and acute pancreatitis (16/20) compared with control patients. The differences between these diagnostic groups and controls were highly significant (P < 0.0001) and independent of pancreatic enzyme activity. Immunochemical analyses of serum pancreatic stone protein showed an isoelectric point (pH 9) similar to that reported for the pancreatic thread protein. With respect to recent communications, these data do not support the etiopathogenic role postulated for pancreatic stone protein in chronic pancreatitis and chronic calcifying pancreatitis by other investigators.