Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, are new markers in Crohn's disease

Dirk Roggenbuck, Dirk Reinhold, Thomas Wex, Alexander Goihl, Ulrike von Arnim, Peter Malfertheiner, Thomas Büttner, Tomas Porstmann, Silvia Porstmann, Bodo Liedvogel, Dimitrios P Bogdanos, Martin W Laass, Karsten Conrad
Clinica Chimica Acta; International Journal of Clinical Chemistry 2011 April 11, 412 (9): 718-24

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by reactivity against microbial and self antigens. Zymogen granule glycoprotein 2 (GP2) was identified as the major autoantigen of CD-specific pancreatic autoantibodies (PAB).

METHODS: Human GP2 was expressed in the Spodoptera frugiperda 9 (Sf9) cell line using the baculovirus system, purified by Ni-chelate chromatography, and used as antigen for anti-GP2 IgA and IgG assessment by enzyme-linked immunosorbent assays (ELISA). Antibodies to mannan of Saccharomyces cerevisiae (ASCA), PAB, and anti-GP2 were investigated in sera of 178 CD patients, 100 ulcerative colitis (UC) patients, and 162 blood donors (BD).

RESULTS: Anti-GP2 IgG and IgA were found in 48/72 (66.7%) and 23/72 (31.9%) PAB positive and 5/106 (4.7%) and 1/106 (0.9%) PAB negative CD patients (p<0.0001), respectively. CD patients displayed significantly higher reactivity to GP2 than UC patients and BD (p<0.0001), respectively. Occurrence of anti-GP2 antibodies correlated with PAB reactivity (Spearmen's rho=0.493, p<0.00001). There was a significant relationship between the occurrence of ASCA IgG and anti-GP2 IgG (p=0.0307).

CONCLUSIONS: Anti-GP2 IgG and IgA constitute novel CD specific autoantibodies, the quantification of which could improve the serological diagnosis of IBD.

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