Pancreatic Autoantibodies Against CUZD1 and GP2 Are Associated with Distinct Clinical Phenotypes of Crohn's Disease.
BACKGROUND
Inflammatory bowel disease (IBD) is characterized by a broad spectrum of clinical phenotypes with different outcomes. In the last decades, several IBD-associated autoantibodies have been identified and investigated for their diagnostic relevance. Autoantibodies against the pancreatic glycoproteins (PAB) CUB and zona pellucida-like domains-containing protein 1 (CUZD1), and glycoprotein 2 (GP2) have been demonstrated to possess high specificity for the diagnosis of IBD. Although several studies have shown significant interrelations of anti-GP2 positivity with disease phenotype, associations of clinical phenotypes with anti-CUZD1 are still unknown. The aim was to identify the association of clinical phenotypes with anti-CUZD1 and anti-GP2 in a well-defined German IBD cohort.


METHODS
Patients with IBD (224 patients with Crohn's disease and 136 patients with ulcerative colitis), who were tested for anti-GP2 and anti-CUZD1 immunoglobulin G and immunoglobulin A by indirect immunofluorescence on transfected cells between 2005 and 2013, were included. Serotype and specified phenotypic data were collected in retrospect and statistically analyzed.


RESULTS
Both anti-GP2 (P < 0.001) and anti-CUZD1 (P < 0.001) were significantly more prevalent in patients with Crohn's disease than in ulcerative colitis. PAB positivity was associated with ileocolonic disease (P = 0.002), perianal disease (P = 0.011), immunosuppressive treatment (P = 0.036), and ASCA positivity (P = 0.036). Anti-CUZD1 positivity was associated with ileocolonic (P = 0.016) and perianal disease (P = 0.002), whereas anti-GP2 positivity was positively associated with stricturing behavior (P = 0.016).


CONCLUSIONS
We found distinct clinical phenotypes to be associated with PAB positivity. Therefore, determination of PABs and their subgroup analysis might identify patients with complicated disease behavior. However, the clinical relevance of our findings should be further evaluated in prospective cohorts.
*Molecular Gastroenterology/Medical Department 1, University Hospital Schleswig Holstein, Campus Lübeck, Germany; †Institute for Anatomy, University of Lübeck, Campus Lübeck, Germany; ‡Department of Experimental Immunology, EUROIMMUN AG, Campus Lübeck, Germany; and §Medical Department 1, Gastroenterology, Institute for Systemic Inflammation Research, University of Lübeck, Campus Lübeck, Germany.
Maike Anna
MA
Michaels
Sebastian Torben
ST
Jendrek
Tobias
T
Korf
Thomas
T
Nitzsche
Bianca
B
Teegen
Lars
L
Komorowski
Stefanie
S
Derer
Torsten
T
Schröder
Florian
F
Baer
Henrik
H
Lehnert
Jürgen
J
Büning
Klaus
K
Fellerman
Christian
C
Sina
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000097:blood* / Q000235:genetics / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D058851:GPI-Linked Proteins / Q000097:blood / Q000276:immunology*; D005858:Germany; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology; D010641:Phenotype
D001323:Autoantibodies; D015415:Biomarkers; C488236:CUZD1 protein, human; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008565:Membrane Proteins