Crohn's disease specific pancreatic antibodies: clinical and pathophysiological challenges.
Crohn's disease (CrD) and ulcerative colitis (UC) are the main inflammatory bowel diseases (IBD). IBD-specific 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.
Dirk
D
Roggenbuck
Dirk
D
Reinhold
Peter
P
Schierack
Dimitrios P
DP
Bogdanos
Karsten
K
Conrad
Martin W
MW
Laass
D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D015551:Autoimmunity; D003424:Crohn Disease / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D010179:Pancreas / Q000276:immunology* / Q000503:physiopathology*
D000906:Antibodies; C489339:GP2 protein, human; D058851:GPI-Linked Proteins