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

Abstract

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.

Increased IgA Glycoprotein-2 Specic Antibody Titres in Refractory Celiac Disease

“…However, analysis of GP2A-IgA levels within CrD subgroups with exclusive colon or ileum localized disease did not substantiate this suggestion. is is in contrast with previous ndings [8,17,18] and may be related to the relatively small group sizes in our study.…”

Anti-hnRNP B1 (RA33) Autoantibodies Are Associated with the Clinical Phenotype in Russian Patients with Rheumatoid Arthritis and Systemic Sclerosis

“…These differences could be due to the different patient characteristics of the respective cohorts or different assay performance of the ELISA employed for autoantibody testing. Indeed, detection of autoantibodies to hnRNP seems to require the preservation of conformational epitopes which can be influenced by the recombinant expression system and coating procedure for ELISA-solid phases utilized as demonstrated for other autoantigenic targets as well [24, 25]. Furthermore, Russian patients with RA can demonstrate different prevalences of RA-specific autoantibodies than reported in studies with Caucasian patients [26].…”

Roles of M cells in infection and mucosal vaccines

“…38 Thus, GP2 on M cells can act as a transcytotic receptor for bacterial antigens, and worthy of note, participate in the mucosal immune responses to these particular bacteria; a subset of commensal and pathogenic enterobacteria (E. coli and S. Typhmurium). 46,47 Other research has shown that a murine GP2 (mGP2)-specific aptamer, isolated using Systematic Evolution of Ligands by EXponential enrichment (SELEX), with a loop structure and the nucleotide sequence, AAAUA (both important for binding to mGP2), binds to mGP2 expressed on the cell surface, indicating that the aptamer serves as a promising tool for testing M-cell-targeted vaccine delivery in murine model systems. 48 …”