The Novel Crohn's Disease Marker Anti-GP2 Antibody Is Associated with Ileocolonic Location of Disease

Somma, Valentina; Ababneh, Hani; Ababneh, Ahmad; Gatti, Simona; Romagnoli, V.; Bendia, E.; Conrad, Karsten; Bogdanos, Dimitrios P.; Roggenbuck, Dirk; Ciarrocchi, Gino

doi:10.1155/2013/683824

Cited by 32 publications

(23 citation statements)

References 51 publications

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“…The link to disease location was confirmed in previous studies showing an association of anti-GP2 with ileal but not colonic CD (19, 20, 33). Interestingly, anti-GP2 can also be detected in higher levels in the serum and feces of patients with ileal-pouch anal anastomosis with pouchitis compared to normal pouch patients (41).…”

Section: Discussionsupporting

confidence: 75%

Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohnʼs Disease

Degenhardt

Dirmeier²,

López

et al. 2016

Inflammatory Bowel Diseases

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Background The presentation of Crohn`s disease (CD) is heterogeneous and often leads to serious complications and need for surgery. We tested serum anti-zymogen granule glycoprotein 2 (GP2) antibodies, including its novel isoform alpha, for association with genetic variants, diagnosis, disease stratification and prediction of CD courses in a combined cross sectional and cohort study. Methods Serum samples of 303 CD, 108 ulcerative colitis (UC), 72 other inflammatory gastrointestinal diseases (OGD) and 206 non GI diseases controls (HC) were tested for the presence of Anti-GP2 and Anti-saccharomyces cervisiae (ASCA) by ELISA. Genetic analysis was performed using the Illumina Immunochip. Results GP2 IgA and IgG had the highest discriminatory capability for CD versus UC and CD versus OGD. We identified an association of GP2 IgA and IgG each with 5 distinct SNPs. Levels of anti-GP2 IgG were moderately associated with ileal disease location. Interestingly, both, anti-GP2 IgA and IgG were exclusively associated with the occurrence of stenosis and need for surgery, independently of disease location, but not with fistulizing CD, early disease onset or disease activity. ASCA IgG and IgA were qualitatively and quantitatively linked to CD, CD complications and need for surgery. Increased levels of ASCA IgG and IgA and positivity for ASCA IgG, but neither levels nor positivity for GP2 IgG or IgA were predictive of the earlier occurrence of complications or surgery. Conclusions Anti-GP2 antibodies may aid as a tool for diagnosis and differentiation of CD and could indicate a more complicated CD course.

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Section: Discussionsupporting

confidence: 75%

Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohnʼs Disease

Degenhardt

Dirmeier²,

López

et al. 2016

Inflammatory Bowel Diseases

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“…PABpositive patients were found to have complicated disease phenotype more frequently as compared with PAB-negative patients in some studies, including the one with the largest IBD cohort [26]. In addition, the presence of anti-GP2 antibodies was associated to stricturing behavior with perianal disease in most [27][28][29] but not all studies [30]. In addition, the presence of anti-GP2 antibodies was associated to stricturing behavior with perianal disease in most [27][28][29] but not all studies [30].…”

Section: Risk For Complicated Disease In Crohn's Disease and Ulceratimentioning

confidence: 97%

Serological studies in inflammatory bowel disease

Papp

Lakatos

2014

Current Opinion in Gastroenterology

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“…Such a differential expression of anti-GP2 could not be confirmed for ASCA which are found elevated in both conditions. According to the Montreal classification of CrD, patients with ileocolonic location have a significantly higher prevalence of anti-GP2, whereas CrD patients with colonic location have been shown to demonstrate a significantly diminished prevalence thereof [88,112]. Furthermore, occurrence of anti-GP2 autoantibodies was significantly more prevalent in CrD patients with young age at onset of disease ( < 16 years).…”

Section: Serology Of Crohn's Disease and Humoral Loss Of Tolerance Tomentioning

confidence: 99%

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

Roggenbuck¹,

Reinhold

Schierack

et al. 2014

Clinical Chemistry and Laboratory Medicine

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Crohn's disease (CrD) and ulcerative colitis (UC) are the main inflammatory bowel diseases (IBD). IBDspecific humoral markers of autoimmunity in the form of autoantibodies have been reported first in the late 1950s by demonstrating the occurrence of autoimmunity in UC, while humoral autoimmunity in CrD can be traced back to the 1970s. Ever since, the pathophysiological role of autoimmune responses in IBDs has remained poorly understood. Notwithstanding, autoreactive responses play a major role in inflammation leading to overt IBD. In CrD, approximately 40% of patients and < 20% of patients with UC demonstrate loss of tolerance to antigens of the exocrine pancreas. Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. The previously unsolved contradiction of pancreatic autoreactivity and intestinal inflammation in IBD was elucidated by demonstrating the expression of GP2 at the site thereof. Intriguingly, GP2 has been reported to be a receptor on microfold cells of intestinal Peyer's patches, which are believed to represent the origin of CrD inflammation. The development of immunoassays for the detection of antibodies to GP2 has paved the way to investigate the association of such antibodies with the clinical phenotype in CrD. Given the recently discovered immunomodulating role of GP2 in innate and adaptive intestinal immunity, this association can shed further light on the pathophysiology of IBD. In this context, the association of anti-GP2 autoantibodies as novel CrD-specific markers with the clinical phenotype in CrD will be discussed in this review.

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The Novel Crohn's Disease Marker Anti-GP2 Antibody Is Associated with Ileocolonic Location of Disease

Cited by 32 publications

References 51 publications

Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohnʼs Disease

Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohnʼs Disease

Serological studies in inflammatory bowel disease

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

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