Serum Pancreatitis-associated Protein Research Articles

Pancreatitis-Associated Protein Does Not Predict Disease Relapse in Inflammatory Bowel Disease Patients

BackgroundThe pancreatitis-associated protein (PAP) is increased in the serum of active inflammatory bowel disease (IBD) patients and its levels seem to be correlated with disease activity. Our aim was to evaluate the usefulness of serum and fecal PAP measurements to predict relapse in patients with inactive IBD.Materials and MethodsWe undertook a 12-month prospective study that included 66 Crohn's disease (CD) and 74 ulcerative colitis (UC) patients. At inclusion, patients were in clinical remission, defined by a Harvey-Bradshaw (HB) Index≤4 (CD) or a partial Mayo Score (MS)<3 (UC), along with a normal serum C reactive protein (CRP) and fecal calprotectin. Patients were followed every 3 months. Blood and stool samples were collected and a clinical evaluation was performed at each visit. Serum PAP and CRP levels as well as fecal concentrations of PAP and calprotectin were assessed.ResultsActive CD patients had an increased mean serum PAP at the diagnosis of the flare (104.1 ng/ml) and 3 months prior to activity (22.68 ng/ml) compared with patients in remission (13.26 ng/ml), p<0.05. No significant change in serum PAP levels in UC and fecal PAP levels in CD and UC were detected during disease activity. In CD, serum PAP was a poor diagnostic predictor of disease activity, with an AUC of 0.69. In patients in remission, fecal PAP was barely detectable in UC compared with CD patients.ConclusionSerum PAP is increased only in active CD patients, but this marker does not predict disease activity. Inactive UC patients have marked low levels of PAP in fecal samples compared with CD patients.

Usefulness of Pancreatitis-Associated Protein, a Novel Biomarker, to Predict Severity of Disease in Ambulatory Patients With Heart Failure

Pancreatitis-associated protein (PAP) is a novel cytokine with putative anti-inflammatory effects. PAP gene expression has been found to be increased in the myocardium of rats with decompensated pressure-overload hypertrophy. A prospective pilot study was performed to test the hypotheses that PAP is elevated in ambulatory patients with heart failure (HF) and that concentrations correlate with the severity of disease. Blood samples were obtained from patients with HF (n = 70) and normal controls (n = 17). Patients with New York Heart Association class III and IV symptoms had a greater mean PAP than patients with class I and II symptoms (35.5 ± 4.0 vs 10.3 ± 1.0 μg/L, p <0.001) and normal controls (35.5 ± 4.0 vs 6.2 ± 0.5 μg/L, p <0.001). Receiver-operating characteristic curves revealed that PAP had similar sensitivity and specificity for HF admission at 6 months as B-type natriuretic peptide and equivalent predictive value for 12-month and 24-month all-cause mortality. On the basis of the receiver-operating characteristic curve analysis, patients were then grouped into those with a serum PAP <24 or ≥24 μg/L. Patients with PAP ≥24 μg/L had significantly worse renal function, greater B-type natriuretic peptide and C-reactive protein levels, higher pulmonary artery systolic pressure, and greater 6- and 24-month all-cause mortality (p <0.05). In conclusion, PAP levels correlate with disease severity in patients with HF and are a marker of cardiorenal syndrome, neurohormonal activation, and elevated filling pressures. PAP is a sensitive and specific marker for increased 6-month HF morbidity and 12- and 24-month all-cause mortality. These results justify the prospective evaluation of PAP as a novel prognostic marker for disease severity in patients with HF.

Pancreatitis-Associated Protein Levels Predict Severity of Disease In Ambulatory Heart Failure Patients

Background: Pancreatitis-associated protein (PAP) is an anti-inflammatory cytokine which is thought to inhibit NF-kB signaling. PAP gene expression is up-regulated in the myocardium of rats with decompensated pressure overload hypertrophy. We performed a prospective pilot study to determine if serum PAP levels predict disease severity in ambulatory heart failure (HF) pts. Methods: Blood was drawn from three groups of HF pts in an ambulatory setting; Group 1 (n = 26) NYHA I–II pts with a left ventricular ejection fraction (LVEF) ≤ 40%, Group 2 (n = 35) NYHA III-IV pts with a LVEF ≤ 40%, and Group 3 (n = 20) NYHA III-IV pts with a LVEF ≥ 50%.

Pancreatitis‐Associated Protein Is Related Closely to Neoplastic Proliferative Activity in Patients with Colorectal Carcinoma

Pancreatitis-associated protein (PAP) is a secretory protein that is not only expressed during acute pancreatitis but also in pancreatic adenocarcinoma, gastric carcinoma, hepatocellular carcinoma, and colorectal carcinoma. Expression in carcinoma might be another characteristic of PAP. The aim of our study was to assess, in 27 patients undergoing surgery for colorectal carcinoma, the expression of the PAP mRNA and to evaluate its association with DNA ploidy and proliferative activity (S-phase fraction, SPF) by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometric analysis (FCM). PAP mRNA was expressed in 29.6% (8 of 27) of the patients with colorectal carcinoma. DNA aneuploid and high SPF were found in 87.5% (7 of 8) of patients with PAP mRNA positive colorectal carcinoma. The serum PAP level was significantly elevated in patients with colorectal carcinoma when compared with the healthy subjects. Twelve of the 27 patients with colorectal carcinoma had high serum PAP concentrations (>25 ng/mL) and the mean SPF was 17.82% +/- 8.02%, which was significantly higher compared with the normal colorectal tissue group (7.33% +/- 3.18%, P < 0.05). The mean serum PAP concentration of DNA aneuploidy colorectal carcinomas was 46.67 +/- 17.58 ng/mL, which was significantly different when compared with the DNA diploidy group (19.18 +/- 8.89 ng/mL, P < 0.05). PAP mRNA expression and serum PAP levels are closely related to neoplastic proliferative activity in patients with colorectal carcinoma. No significant differences are observed between PAP mRNA expression and clinicopathologic parameters (P > 0.05).

Is hyperlipasemia in critically ill patients of clinical importance? An observational CT study

To assess morphological alterations of the pancreas by contrast-enhanced computed tomography (cCT) and subclinical cellular damage of the pancreas by measuring pancreatitis-associated protein (PAP) in critically ill patients without prior pancreatic disorder who presented with raised serum lipase levels. Prospective, observational study Mixed surgical/neurosurgical intensive care unit of a German university hospital. One hundred and thirty consecutive critically ill patients without prior damage or disease of the pancreas and an expected length of stay of more than 5 days. Daily serum lipase measurements and daily serum PAP measurements. Contrast-enhanced upper abdominal cCT study in patients with triple increase of serum lipase. Thirty-eight patients showed raised serum lipase levels and qualified for the cCT scan study. In 20 patients cCT scans were performed. Morphological alterations of the pancreas were found in 7 out these 20 patients while serum PAP levels were raised in all patients. Hyperlipasemia is a common finding in critically ill patients without prior pancreatic disorder. While elevated serum PAP levels indicate pancreatic cellular stress morphological alterations of the pancreas are rare and of little clinical importance.

Pancreatitis-Associated Protein Levels in Pancreatic Juice from Patients with Pancreatic Diseases

Background: Pancreatitis-associated protein (PAP), the acute-phase protein of the pancreas, is overexpressed in acute pancreatitis. Serum PAP levels were reported to be useful as an indicator of the severity, prognosis and healing of acute pancreatitis. Although PAP was originally identified in pancreatic juice, there has been no clinical report on PAP levels in pancreatic juice. This study was conducted to determine levels of PAP in pancreatic juice (PJ-PAP) in various human pancreatic diseases. Methods: PAP levels in endoscopically aspirated PJ were measured by enzyme-linked immunosorbent assay in 86 patients with pancreatic diseases. Results: 55% of 22 patients with pancreatic cancer (PC) and 25% of 49 patients with chronic pancreatitis (CP) were positive (>350 ng/ml) for PJ-PAP. PJ-PAP levels were significantly higher in PC than in CP, in which PJ-PAP was also significantly higher than in 15 control subjects. There was no significant correlation between PJ-PAP and serum PAP, and combination assay of serum PAP and/or PJ-PAP detected 80% of PC cases and 44% of CP cases. Conclusions: We have demonstrated that human PAP could be detected in pancreatic juice from patients with pancreatic diseases. Determination of PAP in pancreatic juice might be helpful for early detection of pancreatic injury.

Pancreatitis‐associated proteins: experimental and clinical studies

Various novel biochemical markers indicate pancreatic cellular injury more accurately than serum amylase or lipase. One of these is a non-enzymatic secretory protein called pancreatitis-associated protein (PAP).The main function of PAP is unclear at present but it may be an acute phase protein in the defence reactions of pancreatic cells. The protein was characterized in 1984 as a serum marker of pancreatitis. The serum PAP is expressed 6 hours after the induction of pancreatitis, and it increases to maximal levels within 2-4 days: PAP is not sufficiently sensitive for the diagnosis of acute pancreatitis in the emergency room. The sensitivity and specificity of PAP in the differentiation of severe from mild pancreatitis is between 60-70%. This is not superior to serum CRP assays or CT scans. PAP increases in pancreatic cellular injury without pancreatitis (subclinical cell damage, graft rejection) where PAP may have a diagnostic role.

Serum Pancreatitis Associated Protein in pretem infants

Serum Pancreatitis Associated Protein in pretem infants

Pancreatitis-associated protein: a putative marker for pancreas graft rejection.

Graft rejection is one of the major causes of graft loss after pancreas transplantation. Pancreatitis-associated protein (PAP) is synthesized by the pancreas due to pancreatic inflammation and has shown to be a good serum marker for injury of the pancreas. It may also be potentially useful in the early recognition of rejection and may thus improve pancreas survival. We retrospectively evaluated PAP as an early serum marker of pancreas graft rejection in a cross-sectional study in which immunohistochemical analysis of pancreas biopsies was undertaken using antibodies against PAP. PAP concentrations were also measured in sera of blood donors and in patients with renal failure, renal replacement therapy, kidney transplantation alone, and simultaneous pancreas-kidney transplantation. All patients had elevated PAP serum levels compared with blood donors (median PAP: 22 ng/ml, range: 5-75 ng/ml; P<0.0001). Patients on renal replacement therapy had higher values than patients with renal failure (median: 420 ng/ml and 150 ng/ml, respectively). There was a strong inverse correlation between PAP levels and creatinine clearance (P<0.001). PAP values in simultaneous pancreas-kidney transplantation patients with histological rejection were significantly higher than values in those who were clinically stable (median: 925 ng/ml and 322 ng/ml, respectively; P=0.006). Rejection was significantly associated with PAP staining of acinar cell surface. There was also a significant correlation between surface positivity of staining and serum PAP levels (P=0.008). No positive PAP staining was observed in concurrently collected biopsies of renal allografts undergoing rejection. Serum PAP levels appear to strongly correlate with creatinine clearance measurements. In patients with a pancreas-kidney transplantation, PAP may prove to be a useful biological and histological marker of pancreatic graft rejection.

Low Serum Pancreatitis-Associated Protein Does not Exclude Complications in Mild Acute Pancreatitis.

Normal serum PAP levels on admission to the hospital in patiens with acute pancreatitis has been proposed to help select the patients who are not going to develop complications. The aims of this study were, first, to assess the specificity of serum pancreatitis associated protein (PAP) serology test and second, to evalute the usefulness of the test for prediciting complications in acute pancreatitis on admission to the hospital. The sensitivity of the PAP ELISA in patiens with acute pancreatitis on admission to the hospital was 70% and the serum PAP levels significantly higher than in healthy controls (p < 0.0001). However, the serum PAP levels in patients with acute pancreatitis were not significantly different from values in patients with various abdominal diseases (p < 0.58). Serum PAP levels gave good correlation to APACHE II (p = 0.02) and CRP (p = 0.01). Two patients with local complications (necrotizing pancreatitis, pancreatic fluid collection) had elevated serum PAP levels on admission to the hospital (> 100 ng/ml). The diagnostic specififity of PAP ELISA is low. Patients, who develop local complications in acute pancreatitis can not be excluded by normal serum PAP levels on admission to the hospital.

Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking?

It has been shown recently that longterm but not short term heavy drinking of alcohol frequently results in increased serum activities of pancreatic enzymes suggesting subclinical pancreatic injury. Serum pancreatitis associated protein (PAP) is a novel protein, whose synthesis in the acinar cells and release into serum is specifically induced by acute pancreatic damage. This study was performed to further characterise the alcohol induced subclinical pancreatic injury by using serum PAP measurements. Three groups were studied: (1) control group (n = 25), (2) short term drinking group (n = 20), who consumed 2.0 g of ethanol per kg body weight during four hours, and (3) longterm drinking group (n = 32), who were admitted to withdrawal clinic after a median 30 months heavy drinking period. Serum PAP concentration was low in the control group (8 (5 to 12) micrograms/l, geometric mean (95% confidence intervals)). In the short term drinking group serum PAP was in the range of the control group values during 56 hours after drinking. Longterm drinking induced at least a 10-fold increase in serum PAP, the highest concentrations being seen on day 2 after drinking had ended (106 (61 to 184) micrograms/l). The patients did not develop abdominal symptoms, increased blood white cell count, or increased serum C reactive protein concentration. These results further support the suggestion that heavy longterm drinking often induces subclinical pancreatic damage, but not clinical pancreatitis.

Serum levels of pancreatitis-associated protein as indicators of the course of acute pancreatitis

Background/Aims: The pancreatitis-associated protein (PAP) is undetectable in normal pancreatic secretion and overexpressed in the acute phase of pancreatitis. We investigated whether serum PAP could be an indicator of the course of acute pancreatitis. Methods: Serum PAP was retrospectively monitored in 98 patients with acute pancreatitis during their stay in the hospital. Patients were classified according to the severity of their disease as group I (≤1 complication), group II (≥2 complications), or group III (lethal pancreatitis). Results: At admission, 34% of patients, all from group I, had normal PAP values (<10 μg/L). None of them developed complications. They had a significantly shorter stay in the hospital than patients with elevated PAP (6.2 days vs. 14.9 days). In all patients, serum PAP increased after admission to a maximum, which correlated significantly to the severity of the disease. Average peak values were 22.2 μg/L and 240.0 μg/L in group I patients with normal or high PAP at admission, 963.0 μg/L and 1436.0 μg/L in groups II and III. Serum PAP decreased steadily during recovery. Conclusions: Monitoring serum PAP in patients with acute pancreatitis would provide (1) at admission, selection of most patients who will not develop complications; (2) a dynamic assessment of severity; and (3) anticipation of the patient's recovery.