Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

Tamas Tornai, Eszter Palyu, Zsuzsanna Vitalis, Istvan Tornai, David Tornai, P. Antal-Szalmás, Gary L. Norman, Zakera Shums, G. Verès, Antal Dezsofi, G. Pár, A. Pár, Peter Orosz, F. Szalay, P. Lakatos, Maria Papp

Research output: Article

10 Citations (Scopus)

Abstract

Aim: To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. Methods: Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various antimicrobial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. Results: A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of antimicrobial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. Conclusion: Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

Original languageEnglish
Pages (from-to)5412-5421
Number of pages10
JournalWorld Journal of Gastroenterology
Volume23
Issue number29
DOIs
Publication statusPublished - aug. 7 2017

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Sclerosing Cholangitis
Immunoglobulin A
Biomarkers
Immunoglobulin G
Enterocytes
Ulcerative Colitis
Antibodies
Fibrosis
Serum
Gliadin
Fatty Acid-Binding Proteins
Mucosal Immunity
Liver
Survival Analysis
Liver Transplantation
Lipopolysaccharides

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis. / Tornai, Tamas; Palyu, Eszter; Vitalis, Zsuzsanna; Tornai, Istvan; Tornai, David; Antal-Szalmás, P.; Norman, Gary L.; Shums, Zakera; Verès, G.; Dezsofi, Antal; Pár, G.; Pár, A.; Orosz, Peter; Szalay, F.; Lakatos, P.; Papp, Maria.

In: World Journal of Gastroenterology, Vol. 23, No. 29, 07.08.2017, p. 5412-5421.

Research output: Article

Tornai, Tamas ; Palyu, Eszter ; Vitalis, Zsuzsanna ; Tornai, Istvan ; Tornai, David ; Antal-Szalmás, P. ; Norman, Gary L. ; Shums, Zakera ; Verès, G. ; Dezsofi, Antal ; Pár, G. ; Pár, A. ; Orosz, Peter ; Szalay, F. ; Lakatos, P. ; Papp, Maria. / Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis. In: World Journal of Gastroenterology. 2017 ; Vol. 23, No. 29. pp. 5412-5421.
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title = "Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis",
abstract = "Aim: To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. Methods: Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67{\%} and cirrhosis: 20{\%}] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various antimicrobial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. Results: A total of 28.4{\%}, 28.0{\%}, 9{\%} and 20.9{\%} of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of antimicrobial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. Conclusion: Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.",
keywords = "Anti-F-actin antibody, Anti-gliadin antibody, Gut barrier dysfunction, Intestinal fatty acid-binding protein, Primary sclerosing cholangitis",
author = "Tamas Tornai and Eszter Palyu and Zsuzsanna Vitalis and Istvan Tornai and David Tornai and P. Antal-Szalm{\'a}s and Norman, {Gary L.} and Zakera Shums and G. Ver{\`e}s and Antal Dezsofi and G. P{\'a}r and A. P{\'a}r and Peter Orosz and F. Szalay and P. Lakatos and Maria Papp",
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TY - JOUR

T1 - Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

AU - Tornai, Tamas

AU - Palyu, Eszter

AU - Vitalis, Zsuzsanna

AU - Tornai, Istvan

AU - Tornai, David

AU - Antal-Szalmás, P.

AU - Norman, Gary L.

AU - Shums, Zakera

AU - Verès, G.

AU - Dezsofi, Antal

AU - Pár, G.

AU - Pár, A.

AU - Orosz, Peter

AU - Szalay, F.

AU - Lakatos, P.

AU - Papp, Maria

PY - 2017/8/7

Y1 - 2017/8/7

N2 - Aim: To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. Methods: Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various antimicrobial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. Results: A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of antimicrobial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. Conclusion: Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

AB - Aim: To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. Methods: Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various antimicrobial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. Results: A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of antimicrobial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. Conclusion: Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

KW - Anti-F-actin antibody

KW - Anti-gliadin antibody

KW - Gut barrier dysfunction

KW - Intestinal fatty acid-binding protein

KW - Primary sclerosing cholangitis

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