Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn's disease

被引：107

作者：

Roggenbuck, D. ^{[2
]}

Hausdorf, G. ^{[3
]}

Martinez-Gamboa, L. ^{[3
]}

Reinhold, D. ^{[4
]}

Buettner, T. ^{[2
]}

Jungblut, P. R. ^{[5
]}

Porstmann, T. ^{[6
]}

Laass, M. W. ^{[7
]}

Henker, J. ^{[7
]}

Buening, C. ^{[8
]}

Feist, E. ^{[3
]}

Conrad, K. ^{[1
]}

机构：

[1] Tech Univ Dresden, Inst Immunol, D-01307 Dresden, Germany

[2] GA Gener Assays GmbH, Dahlewitz, Germany

[3] Charite, Dept Rheumatol & Clin Immunol, D-13353 Berlin, Germany

[4] Univ Magdeburg, Inst Mol & Clin Immunol, D-39106 Magdeburg, Germany

[5] Max Planck Inst Infect Biol, Berlin, Germany

[6] Seramun Diagnost GmbH, Heidesee, Germany

[7] Tech Univ Dresden, Pediat Clin, D-01307 Dresden, Germany

[8] Charite, Dept Gastroenterol Hepatol & Endocrinol, D-13353 Berlin, Germany

来源：

GUT | 2009年 / 58卷 / 12期

关键词：

INFLAMMATORY-BOWEL-DISEASE; ANCHORED PROTEINS; ESCHERICHIA-COLI; PEYERS-PATCHES; RAT PANCREAS; SELF-BINDING; GENE FAMILY; M-CELLS; MARKERS; GP-2;

D O I：

10.1136/gut.2008.162495

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Backround and aims: The aetiopathogenesis of Crohn's disease, an inflammatory bowel disease (IBD), is not yet fully understood. Autoimmune mechanisms are thought to play a role in the development of Crohn's disease, but the target antigens and the underlying pathways have not been sufficiently identified. Methods: Based on data from immunoblotting and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry, the major antigenic target of pancreatic autoantibodies (PABs), which are specific for Crohn's disease, was identified. Specificity of autoantibody reactivity was confirmed by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) using purified rat and human recombinant GP2 synthesised in transiently transfected mammalian HEK 293 cells. Real-time polymerase chain reaction (rt-PCR) and IIF were used to detect mRNA and antigen localisation in human colon biopsies. Results: The major zymogen granule membrane glycoprotein 2 (GP2) was identified as the autoantigen of PABs in Crohn's disease. PAB-positive sera from patients with Crohn's disease (n = 42) displayed significantly higher IgG reactivity to rat GP2 in ELISA than either PAB-negative sera (n = 31), or sera from patients with ulcerative colitis (n = 49), or sera from blood donors (n = 69) (p < 0.0001, respectively). Twenty-eight (66%) and 18 (43%) of 42 PAB-positive sera demonstrated IgG and IgA reactivity to human recombinant GP2 in IIF, respectively. Patients with PAB-negative Crohn's disease (n = 31) were not reactive. GP2 mRNA transcription was significantly higher in colon biopsies from patients with Crohn's disease (n = 4) compared to patients with ulcerative colitis (n = 4) (p = 0.0286). Immunochemical staining confirmed GP2 expression in human colon biopsies from patients with Crohn's disease. Conclusion: Anti-GP2 autoantibodies constitute novel Crohn's disease-specific markers, the quantification of which could significantly improve the serological diagnosis of IBD. The expression of GP2 in human enterocytes suggests an important role for anti-GP2 response in the pathogenesis of Crohn's disease.

引用

页码：1620 / 1628

页数：9

共 45 条

[1] Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease [J].