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Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype

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Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype. / Sowa, Mandy; Kolenda, Rafał; Baumgart, Daniel C; Pratschke, Johann; Papp, Maria; Tornai, Tamas; Suchanski, Jaroslaw; Bogdanos, Dimitrios P; Mytilinaiou, Maria G; Hammermann, Jutta; Laass, Martin W; Conrad, Karsten; Schramm, Christoph; Franke, Andre; Roggenbuck, Dirk; Schierack, Peter.

In: FRONT IMMUNOL, Vol. 9, 2018, p. 1959.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sowa, M, Kolenda, R, Baumgart, DC, Pratschke, J, Papp, M, Tornai, T, Suchanski, J, Bogdanos, DP, Mytilinaiou, MG, Hammermann, J, Laass, MW, Conrad, K, Schramm, C, Franke, A, Roggenbuck, D & Schierack, P 2018, 'Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype', FRONT IMMUNOL, vol. 9, pp. 1959. https://doi.org/10.3389/fimmu.2018.01959

APA

Sowa, M., Kolenda, R., Baumgart, D. C., Pratschke, J., Papp, M., Tornai, T., Suchanski, J., Bogdanos, D. P., Mytilinaiou, M. G., Hammermann, J., Laass, M. W., Conrad, K., Schramm, C., Franke, A., Roggenbuck, D., & Schierack, P. (2018). Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype. FRONT IMMUNOL, 9, 1959. https://doi.org/10.3389/fimmu.2018.01959

Vancouver

Sowa M, Kolenda R, Baumgart DC, Pratschke J, Papp M, Tornai T et al. Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype. FRONT IMMUNOL. 2018;9:1959. https://doi.org/10.3389/fimmu.2018.01959

Bibtex

@article{fa8d1826c1ef4fc0aae7d541f4f3e69c,
title = "Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype",
abstract = "Introduction: Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP21-4) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP21-4 and their association with the PSC phenotype for risk prediction were examined. Methods: GP2 isoforms were stably expressed as glycosylphosphatidyl - inositol-anchored molecules in the membrane of HEp-2 cells and used as autoantigenic targets in indirect immunofluorescence assay (IFA). aGP21-4 IgA and IgG were detected by IFA in 212 PSC patients of four European university hospitals and 145 controls comprising 95 patients with cystic fibrosis and 50 healthy subjects. Results: Combined aGP21 and aGP24 IgA testing with a sensitivity of 66.0% and a specificity of 97.9% resulted in the best diagnostic performance (Youden index: 0.64) regarding all aGP2 and combinations thereof. aGP24 IgA positivity is significantly associated with the presence of cirrhosis in PSC (p = 0.0056). Logistic regression revealed the occurrence of aGP21 IgA (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.03-1.86) and aGP24 IgA (OR 1.52, 95%CI: 1.07-2.15) along with male gender (OR 0.51, 95%CI: 0.27-0.97) and older age (OR 1.03 95%CI: 1.01-1.05) as significant risks for the concomitant presence of cirrhosis in PSC. Conclusions: Combined aGP21 and aGP24 IgA analysis is preferred to single aGP2 isoform analysis for sensitive PSC autoantibody testing. Positivity for aGP21 and aGP24 IgA is associated with cirrhosis in PSC and could be used for risk stratification.",
keywords = "Journal Article",
author = "Mandy Sowa and Rafa{\l} Kolenda and Baumgart, {Daniel C} and Johann Pratschke and Maria Papp and Tamas Tornai and Jaroslaw Suchanski and Bogdanos, {Dimitrios P} and Mytilinaiou, {Maria G} and Jutta Hammermann and Laass, {Martin W} and Karsten Conrad and Christoph Schramm and Andre Franke and Dirk Roggenbuck and Peter Schierack",
year = "2018",
doi = "10.3389/fimmu.2018.01959",
language = "English",
volume = "9",
pages = "1959",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype

AU - Sowa, Mandy

AU - Kolenda, Rafał

AU - Baumgart, Daniel C

AU - Pratschke, Johann

AU - Papp, Maria

AU - Tornai, Tamas

AU - Suchanski, Jaroslaw

AU - Bogdanos, Dimitrios P

AU - Mytilinaiou, Maria G

AU - Hammermann, Jutta

AU - Laass, Martin W

AU - Conrad, Karsten

AU - Schramm, Christoph

AU - Franke, Andre

AU - Roggenbuck, Dirk

AU - Schierack, Peter

PY - 2018

Y1 - 2018

N2 - Introduction: Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP21-4) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP21-4 and their association with the PSC phenotype for risk prediction were examined. Methods: GP2 isoforms were stably expressed as glycosylphosphatidyl - inositol-anchored molecules in the membrane of HEp-2 cells and used as autoantigenic targets in indirect immunofluorescence assay (IFA). aGP21-4 IgA and IgG were detected by IFA in 212 PSC patients of four European university hospitals and 145 controls comprising 95 patients with cystic fibrosis and 50 healthy subjects. Results: Combined aGP21 and aGP24 IgA testing with a sensitivity of 66.0% and a specificity of 97.9% resulted in the best diagnostic performance (Youden index: 0.64) regarding all aGP2 and combinations thereof. aGP24 IgA positivity is significantly associated with the presence of cirrhosis in PSC (p = 0.0056). Logistic regression revealed the occurrence of aGP21 IgA (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.03-1.86) and aGP24 IgA (OR 1.52, 95%CI: 1.07-2.15) along with male gender (OR 0.51, 95%CI: 0.27-0.97) and older age (OR 1.03 95%CI: 1.01-1.05) as significant risks for the concomitant presence of cirrhosis in PSC. Conclusions: Combined aGP21 and aGP24 IgA analysis is preferred to single aGP2 isoform analysis for sensitive PSC autoantibody testing. Positivity for aGP21 and aGP24 IgA is associated with cirrhosis in PSC and could be used for risk stratification.

AB - Introduction: Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP21-4) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP21-4 and their association with the PSC phenotype for risk prediction were examined. Methods: GP2 isoforms were stably expressed as glycosylphosphatidyl - inositol-anchored molecules in the membrane of HEp-2 cells and used as autoantigenic targets in indirect immunofluorescence assay (IFA). aGP21-4 IgA and IgG were detected by IFA in 212 PSC patients of four European university hospitals and 145 controls comprising 95 patients with cystic fibrosis and 50 healthy subjects. Results: Combined aGP21 and aGP24 IgA testing with a sensitivity of 66.0% and a specificity of 97.9% resulted in the best diagnostic performance (Youden index: 0.64) regarding all aGP2 and combinations thereof. aGP24 IgA positivity is significantly associated with the presence of cirrhosis in PSC (p = 0.0056). Logistic regression revealed the occurrence of aGP21 IgA (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.03-1.86) and aGP24 IgA (OR 1.52, 95%CI: 1.07-2.15) along with male gender (OR 0.51, 95%CI: 0.27-0.97) and older age (OR 1.03 95%CI: 1.01-1.05) as significant risks for the concomitant presence of cirrhosis in PSC. Conclusions: Combined aGP21 and aGP24 IgA analysis is preferred to single aGP2 isoform analysis for sensitive PSC autoantibody testing. Positivity for aGP21 and aGP24 IgA is associated with cirrhosis in PSC and could be used for risk stratification.

KW - Journal Article

U2 - 10.3389/fimmu.2018.01959

DO - 10.3389/fimmu.2018.01959

M3 - SCORING: Journal article

C2 - 30233574

VL - 9

SP - 1959

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -