Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis

Tamas Tornai, David Tornai, Nora Sipeki, Istvan Tornai, Rayan Alsulaimani, Kai Fechner, Dirk Roggenbuck, Gary L. Norman, G. Verès, G. Pár, A. Pár, F. Szalay, P. Lakatos, P. Antal-Szalmás, M. Papp

Research output: Article

1 Citation (Scopus)

Abstract

Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn's disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9-99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05-21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target.

Original languageEnglish
Article number399
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - dec. 1 2018

Fingerprint

Sclerosing Cholangitis
Immunity
Glycoproteins
Immunoglobulin A
Autoantibodies
Proteins
Secretory Component
Bacterial Translocation
Secretory Immunoglobulin A
Antibodies
Indirect Fluorescent Antibody Technique
Innate Immunity
Crohn Disease
Liver Diseases
Anti-Idiotypic Antibodies
Flow Cytometry
Mucous Membrane
Chronic Disease
Transplants
Survival

ASJC Scopus subject areas

  • General

Cite this

Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis. / Tornai, Tamas; Tornai, David; Sipeki, Nora; Tornai, Istvan; Alsulaimani, Rayan; Fechner, Kai; Roggenbuck, Dirk; Norman, Gary L.; Verès, G.; Pár, G.; Pár, A.; Szalay, F.; Lakatos, P.; Antal-Szalmás, P.; Papp, M.

In: Scientific Reports, Vol. 8, No. 1, 399, 01.12.2018.

Research output: Article

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abstract = "Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn's disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2{\%}) compared to controls(healthy:0{\%} and CLD:4.5{\%}), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8{\%} (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4{\%} (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9-99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05-21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target.",
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AU - Tornai, Tamas

AU - Tornai, David

AU - Sipeki, Nora

AU - Tornai, Istvan

AU - Alsulaimani, Rayan

AU - Fechner, Kai

AU - Roggenbuck, Dirk

AU - Norman, Gary L.

AU - Verès, G.

AU - Pár, G.

AU - Pár, A.

AU - Szalay, F.

AU - Lakatos, P.

AU - Antal-Szalmás, P.

AU - Papp, M.

PY - 2018/12/1

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