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 language | English |
|---|---|
| Article number | 399 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - dec. 1 2018 |
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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
}
TY - JOUR
T1 - Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis
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
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040450338&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040450338&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-18622-1
DO - 10.1038/s41598-017-18622-1
M3 - Article
C2 - 29321484
AN - SCOPUS:85040450338
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 399
ER -