- Email: [email protected]
Low aminotransferases levels in active Crohn's disease
Category 9: Immunology, autoimmune liver disease ~57
Pathology; 2Dept of Surg and Oncological Sciences, University of Padova, Italy Several pathogenic mechanisms in PBC have recently been proposed, including the role of T cell-mediated cytotoxicity and the intracellular interaction between the IgA class of AMA and mitochondrial autoantigens. Furthermore, IgA class plays a major role in mucosal defences against several antigens. Aim: To evaluate the role of IgA transport in duodenal mucosa of PBC. Methods: 25 pts with PBC and normal serum IgA levels underwent upper endoscopy for clinical purposes (22 F, 3 M, 9 having histological stage II, 7 stage III, and 9 stage IV). During endoscopy 7 distal duodenum biopsies were taken and processed for: i) microscopic assessment; ii) immunohistochemical staining using polyclonal anti-IgA (Dako, Glostrup, Denmark), and anti-human IgA secretory component [IgA-SC] (Sigma, Poole, Dorset, UK); iii) in-vitro organ culture system; 5 pts with functional dyspepsia served as controls. Results: The enterocyte height was always normal (mean 35.3 4- 3.4 /zm) and brush border was well defined. Lymphangectasia of the assial vessel was observed in 11 cases (mild in 7, moderate in 4). Enterocytes in the villi and epithelial cells in the crypt from 24/25 PBC pts showed a marked reduction of IgA-SC compared to controls; conversely, in 22/25 PBC pts an increase in IgA staining along the basolateral site of enterocyte membrane was observed, resulting in widening of cell to cell junction. In the culture system the mean of enterocyte height in PBC did not differ from controls (35.3 4- 3.4 # m in PBC vs 34.4 4- 3.2 in controls at baseline, 28.1 4- 2.7 # m in PBC vs 28.9 4- 2.3 in controls after 24 hrs. Conclusions: An in-situ-defect of IgA secretion may be suggested, possibly a defect in binding of IgA-SC to the polymeric IgA receptor. As consequence, the defect of mucosal IgA might alter the mucosal immunity, allowing several antigens to adhering and penetrating the epithelium.
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-'1 HEPATIC EXPRESSION OF SECONDARY LYMPHOID CHEMOKINE MAY PROMOTE THE RECRUITMENT OF A4B7+ LYMPHOCYTES TO THE LIVER
DEFECT OF MUCOSAL IgA IN PRIMARY BILIARY CIRRHOSIS (PBC)
A. Floreani, A. Baragiotta, D. Pizzuti, D. Martines, A. Cecchetto 1, S. Chiarelli 2. ~Dept of Surg and Gastroenterol Sci, Institute of
LOW AMINOTRANSFERASES LEVELS IN ACTIVE CROHN'S DISEASE
Y. Bujanover, A. Fradkin, I. Weintraub, B.A. Sela, B. Weiss. Pediatrics,
Sheba Medical Center, Tel Hashomer, Israel Background: Pyridoxin is an important co factor in aminotransferases (AT) activity. We observed low serum AT levels in active Crohn's disease (CD) patients. Pyridoxin deficiency was not described in this group of patients before. Aim: To investigate the possibility that pyridoxin deficiency in CD patients is the cause for the low serum AT observed in those patients. Methods: Sixteen CD patients were studied, 4 female and 12 male, age range 11-25 y (M 15 Y). CD activity was assessed using CDAI. The following laboratory parameters-CBC, ESR, CRP, ALB, Fe, TIBC, Zn, folic acid, B12, and AST were determined by known conventional methods. Pyridoxin levels were determined by BPLC. A group of 30 age matched healthy individuals served as a control group. Results: Pyridoxin levels were significantly lower in the active CD group 5-180 nmol/1 (M 41) relative to controls 29-224 nmol/l (M 68). Nine out of the 16 CD patients had very low to low border line levels 5-26 nmol/1. This group had also significanly lower levels of AST (7-20 IU/L) relative to the controls (>20 IU/L). Patients with low pyridoxin and AST levels had CDAI OF 200 and above. Conclusions: Low AST serum levels in active CD patients is common. Low AST levels are commonly associated with pyridoxin deficiency. Supplement of pyridoxin should be a practice in the treatment of CD patients. Pyridoxin supplement may improve liver function, is commo
213
D.H. Adams, A.J. Grant, C. Walker, S. Goddard. Hepatology, MRC
Centrefor Immune Regulation, Solihull WestMidlands, UK Background: Mucosal adressin cell adhesion molecule (MAdCAM-1) on endothelium and the integrin a4b7 on gut activated lymphocytes, are crucial in establishing lymphocyte homing patterns. Secondary lymphoid chemokine (SLC) expressed on lymph node HEV's, is reported to stimulate a4b7 mediated lymphocyte adhesion to MAdCAM-1 and blockade of the SLC receptor, CCR7 inhibits T-cell recruitment to Peyer's patch HEV's. We have previously described the presence of functionally active MAdCAM-1 in chronic inflammatory liver diseases but the induction of SLC in liver disease has not been reported. Method & Results: SLC was detected immunohistochemically in normal human liver, in association with dendritic cells in portal tracts, and on portal vein endothelium in chronic inflammatory liver disease. We used flow cytometry of liver-derived lymphocytes to determine the expression of CCR7 on liver-infiltrating T-cells. A small population of CD3+CCR7+ T-cells was detected in normal liver but in primary sclerosing cholangitis up to 20% of T cells were positive. As SLC is chemotactic for naive T-cells we determined expression of the naive cell marker CD45RA. FACS analysis demonstrated that 80% of the a4b7+ T cells in peripheral blood and 45% of the a4b7+ T cells in the liver were CD45RA+. Chemotaxis assays demonstrated the ability of a4b7+ peripheral blood lymphocytes from normal volunteers to migrate to SLC. Summary: SLC is demonstrable on hepatic portal endothelium and in association with dendritic cells in chronic inflammatory liver disease. The expression of CCR7 on both peripheral blood and liver derived a4b7+/CD45RA+ lymphocytes suggests that SLC could be attracting this subset of T cells from the circulation and retaining them at sites of chronic inflammation within the liver.
•7
SERUM CYTOKINE LEVELS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: EFFECT OF TREATMENT WITH URSODEOXYCHOLIC ACID
M.G. Neuman, P. Angulo, I.M. Malkiewicz, R.A. Jorgensen, G.G. Katz, J.P. De Silva, K.D. Lindor. Clinical Pharmacology, Sunnybrook
WCHSC and Mayo Clinic Foundation, Rochester, MN, USA Aims: 1- to measure serum tumor necrosis alpha (TNFa) as marker of liver inflammation and tumor growth factor beta (TGFb) as marker of collagenization in primary sclerosing cholangitis (PSC)-patients; 2-to correlate with the severity of the disease and 3-to see the effect of therapy with ursodeoxycholic acid UDCA Methods: 30 PSC patients with inactive IBD received a-15 or b-25 mg/day UDCA for 2 years. Serum TNFa and TGFb were measured at time 0 and at the end of therapy (1). Results: At baseline, serum levels of TNF-correlated positively with levels of bilirubin (p < 0.03), and Mayo risk score (p = 0.002) and negatively with levels of albumin (p < 0.03). Levels of TGF-a correlated positively with albumin levels (p < 0.05) and negatively with bilirubin levels (p < 0.02) and Mayo risk score (p = 0.004). Conclusions: Serum levels of TNF-a) reflects the severity of the liver disease while TGF-b fibrinogenic activity may be of major relevance in earlier PSC. UDCA improves liver biochemistries and Mayo risk score in patients with PSC independently of changes in the cytokine milieu.
Pathology; 2Dept of Surg and Oncological Sciences, University of Padova, Italy Several pathogenic mechanisms in PBC have recently been proposed, including the role of T cell-mediated cytotoxicity and the intracellular interaction between the IgA class of AMA and mitochondrial autoantigens. Furthermore, IgA class plays a major role in mucosal defences against several antigens. Aim: To evaluate the role of IgA transport in duodenal mucosa of PBC. Methods: 25 pts with PBC and normal serum IgA levels underwent upper endoscopy for clinical purposes (22 F, 3 M, 9 having histological stage II, 7 stage III, and 9 stage IV). During endoscopy 7 distal duodenum biopsies were taken and processed for: i) microscopic assessment; ii) immunohistochemical staining using polyclonal anti-IgA (Dako, Glostrup, Denmark), and anti-human IgA secretory component [IgA-SC] (Sigma, Poole, Dorset, UK); iii) in-vitro organ culture system; 5 pts with functional dyspepsia served as controls. Results: The enterocyte height was always normal (mean 35.3 4- 3.4 /zm) and brush border was well defined. Lymphangectasia of the assial vessel was observed in 11 cases (mild in 7, moderate in 4). Enterocytes in the villi and epithelial cells in the crypt from 24/25 PBC pts showed a marked reduction of IgA-SC compared to controls; conversely, in 22/25 PBC pts an increase in IgA staining along the basolateral site of enterocyte membrane was observed, resulting in widening of cell to cell junction. In the culture system the mean of enterocyte height in PBC did not differ from controls (35.3 4- 3.4 # m in PBC vs 34.4 4- 3.2 in controls at baseline, 28.1 4- 2.7 # m in PBC vs 28.9 4- 2.3 in controls after 24 hrs. Conclusions: An in-situ-defect of IgA secretion may be suggested, possibly a defect in binding of IgA-SC to the polymeric IgA receptor. As consequence, the defect of mucosal IgA might alter the mucosal immunity, allowing several antigens to adhering and penetrating the epithelium.
-~
-'1 HEPATIC EXPRESSION OF SECONDARY LYMPHOID CHEMOKINE MAY PROMOTE THE RECRUITMENT OF A4B7+ LYMPHOCYTES TO THE LIVER
DEFECT OF MUCOSAL IgA IN PRIMARY BILIARY CIRRHOSIS (PBC)
A. Floreani, A. Baragiotta, D. Pizzuti, D. Martines, A. Cecchetto 1, S. Chiarelli 2. ~Dept of Surg and Gastroenterol Sci, Institute of
LOW AMINOTRANSFERASES LEVELS IN ACTIVE CROHN'S DISEASE
Y. Bujanover, A. Fradkin, I. Weintraub, B.A. Sela, B. Weiss. Pediatrics,
Sheba Medical Center, Tel Hashomer, Israel Background: Pyridoxin is an important co factor in aminotransferases (AT) activity. We observed low serum AT levels in active Crohn's disease (CD) patients. Pyridoxin deficiency was not described in this group of patients before. Aim: To investigate the possibility that pyridoxin deficiency in CD patients is the cause for the low serum AT observed in those patients. Methods: Sixteen CD patients were studied, 4 female and 12 male, age range 11-25 y (M 15 Y). CD activity was assessed using CDAI. The following laboratory parameters-CBC, ESR, CRP, ALB, Fe, TIBC, Zn, folic acid, B12, and AST were determined by known conventional methods. Pyridoxin levels were determined by BPLC. A group of 30 age matched healthy individuals served as a control group. Results: Pyridoxin levels were significantly lower in the active CD group 5-180 nmol/1 (M 41) relative to controls 29-224 nmol/l (M 68). Nine out of the 16 CD patients had very low to low border line levels 5-26 nmol/1. This group had also significanly lower levels of AST (7-20 IU/L) relative to the controls (>20 IU/L). Patients with low pyridoxin and AST levels had CDAI OF 200 and above. Conclusions: Low AST serum levels in active CD patients is common. Low AST levels are commonly associated with pyridoxin deficiency. Supplement of pyridoxin should be a practice in the treatment of CD patients. Pyridoxin supplement may improve liver function, is commo
213
D.H. Adams, A.J. Grant, C. Walker, S. Goddard. Hepatology, MRC
Centrefor Immune Regulation, Solihull WestMidlands, UK Background: Mucosal adressin cell adhesion molecule (MAdCAM-1) on endothelium and the integrin a4b7 on gut activated lymphocytes, are crucial in establishing lymphocyte homing patterns. Secondary lymphoid chemokine (SLC) expressed on lymph node HEV's, is reported to stimulate a4b7 mediated lymphocyte adhesion to MAdCAM-1 and blockade of the SLC receptor, CCR7 inhibits T-cell recruitment to Peyer's patch HEV's. We have previously described the presence of functionally active MAdCAM-1 in chronic inflammatory liver diseases but the induction of SLC in liver disease has not been reported. Method & Results: SLC was detected immunohistochemically in normal human liver, in association with dendritic cells in portal tracts, and on portal vein endothelium in chronic inflammatory liver disease. We used flow cytometry of liver-derived lymphocytes to determine the expression of CCR7 on liver-infiltrating T-cells. A small population of CD3+CCR7+ T-cells was detected in normal liver but in primary sclerosing cholangitis up to 20% of T cells were positive. As SLC is chemotactic for naive T-cells we determined expression of the naive cell marker CD45RA. FACS analysis demonstrated that 80% of the a4b7+ T cells in peripheral blood and 45% of the a4b7+ T cells in the liver were CD45RA+. Chemotaxis assays demonstrated the ability of a4b7+ peripheral blood lymphocytes from normal volunteers to migrate to SLC. Summary: SLC is demonstrable on hepatic portal endothelium and in association with dendritic cells in chronic inflammatory liver disease. The expression of CCR7 on both peripheral blood and liver derived a4b7+/CD45RA+ lymphocytes suggests that SLC could be attracting this subset of T cells from the circulation and retaining them at sites of chronic inflammation within the liver.
•7
SERUM CYTOKINE LEVELS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: EFFECT OF TREATMENT WITH URSODEOXYCHOLIC ACID
M.G. Neuman, P. Angulo, I.M. Malkiewicz, R.A. Jorgensen, G.G. Katz, J.P. De Silva, K.D. Lindor. Clinical Pharmacology, Sunnybrook
WCHSC and Mayo Clinic Foundation, Rochester, MN, USA Aims: 1- to measure serum tumor necrosis alpha (TNFa) as marker of liver inflammation and tumor growth factor beta (TGFb) as marker of collagenization in primary sclerosing cholangitis (PSC)-patients; 2-to correlate with the severity of the disease and 3-to see the effect of therapy with ursodeoxycholic acid UDCA Methods: 30 PSC patients with inactive IBD received a-15 or b-25 mg/day UDCA for 2 years. Serum TNFa and TGFb were measured at time 0 and at the end of therapy (1). Results: At baseline, serum levels of TNF-correlated positively with levels of bilirubin (p < 0.03), and Mayo risk score (p = 0.002) and negatively with levels of albumin (p < 0.03). Levels of TGF-a correlated positively with albumin levels (p < 0.05) and negatively with bilirubin levels (p < 0.02) and Mayo risk score (p = 0.004). Conclusions: Serum levels of TNF-a) reflects the severity of the liver disease while TGF-b fibrinogenic activity may be of major relevance in earlier PSC. UDCA improves liver biochemistries and Mayo risk score in patients with PSC independently of changes in the cytokine milieu.