Pancreatitis-Associated Protein in Patients with Celiac Disease: Serum Levels and Immunocytochemical Localization in Small Intestine

Abstract

Since PAP is a stress protein expressed in human pancreas during pancreatitis but also constitutively synthesized in the small intestine, we looked whether its expression would be altered in patients with celiac disease. Serum PAP concentrations were determined consecutively in 54 patients with celiac disease on a free diet (group A), in 47 patients with celiac disease on a gluten-free diet (group B), in 22 patients with other intestinal pathologies but with normal intestinal mucosa (group C), in 14 patients with retarded growth, no gastrointestinal disease and normal intestinal mucosa (group D), and in 17 controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A (127.3 ± 56.8) than in the other groups (B: 47.2 ± 20.5; C: 51.5 ± 32.2; D: 47 ± 22.8; E: 27.6 ± 9.0), which were not different from each other. In group A, a positive correlation was observed between serum PAP values and antigluten antibody levels (vs. AGA IgG r – 0.58, p < 0.001; vs. AGA IgA r = 0.66, p < 0.001). Furthermore, 12 patients from group A were evaluated after 10-12 months of gluten-free diet and in all of them PAP serum concentration had decreased (mean ± SE before the diet 122.5 ± 36.4, after the diet 48.7 ± 13.7, p < 0.0001). In addition, we performed an immunocytochemical study to localize PAP in the intestinal mucosa of patients from all groups except E. PAP was localized to the Paneth cells and to some globet cells, in patients with mucosal atrophy as well as in those with normal mucosa with no obvious quantitative difference. We concluded that in patients with celiac disease the active phase of the disease was accompanied by an increased serum concentration of PAP. Further studies are necessary to understand the mechanism leading to PAP elevation in the serum of patients with celiac disease.

Ileal Mucosal and Fecal Pancreatitis Associated Protein Levels Reflect Severity of Salmonella Infection in Rats

“…In support of findings reported [7,20,25], our experiments clearly showed that PAP/RegIII protein was present in enterocytes at the crypt-villus junction of the ileal mucosa. The protein was not detected in the goblet cells, goblet cell thecae, or Paneth cells.…”

Expression analysis of the regenerating gene (Reg) family members Reg‐IIIβ and Reg‐IIIγ in the mouse during development

“…Reg-IIIb mRNA expression was located at the lower villus and upper crypt, suggesting the possibility that Reg-IIIb-expressing cells were relatively newly differentiated or perhaps immature absorptive cells, but not Paneth cells. This profile was partially consistent with that of PAP-I (Reg-IIIbeta in mouse) (Chakraborty et al, 1995b), although in human, hepatocarcinoma-intestinepancreas/pancreatitis-associated protein (HIP/PAP, corresponding to Reg-III) was reportedly located in Paneth cells from patients with celiac disease or inflammatory bowel disease (Carroccio et al, 1997;Gironella et al, 2005). In contrast, Paneth cells did express Reg-IIIc as described in a previous report (Cash et al, 2006).…”

Clinical Evaluation of Pancreatitis-Associated Protein as a Serum Marker of Hepatocellular Carcinoma: Comparison with α-Fetoprotein

“…Also molecules such as ferritin, carbohydrate antigen 19-9, immune complexes and monoclonal antibodies are no improvement on the simple AFP assay [20][21][22][23]. PAP is a protein of pancreatic origin [8] but is also produced by intestinal cells [24] and its gene is activated in the liver during carcinogenesis [10,11]. This study consequently aimed to evaluate its usefulness as a marker of HCC.…”