Identification of a novel autoantigen in inflammatory bowel disease by protein microarray

N Vermeulen, KO de Beeck, S Vermeire… - Inflammatory bowel …, 2011 - academic.oup.com
N Vermeulen, KO de Beeck, S Vermeire, K Van Steen, G Michiels, V Ballet, P Rutgeerts…
Inflammatory bowel diseases, 2011academic.oup.com
Background Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-
antigens and microbial antigens. We used a protein microarray approach to identify novel
autoantigens in IBD. Methods ProtoArray Human Protein Microarray v4. 0 containing 8268
human proteins from Invitrogen (La Jolla, CA) was used. Results Twenty-five IBD patients
and five healthy controls were screened for candidate autoantigens. For 256 antigens, IBD
patients had a higher seroreactivity than controls. Twenty antigens were selected for further …
Background
Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and microbial antigens. We used a protein microarray approach to identify novel autoantigens in IBD.
Methods
ProtoArray Human Protein Microarray v4.0 containing 8268 human proteins from Invitrogen (La Jolla, CA) was used.
Results
Twenty-five IBD patients and five healthy controls were screened for candidate autoantigens. For 256 antigens, IBD patients had a higher seroreactivity than controls. Twenty antigens were selected for further evaluation in a larger cohort (60 ulcerative colitis [UC] patients, 60 Crohn's disease [CD] patients, 60 healthy controls, and 60 gastrointestinal-diseased controls) by means of a customized protein microarray. Out of these 20 antigens, one antigen, family with sequence similarity 84 member A (FAM84A), was identified as a target antigen in IBD. Antibodies to FAM84A were significantly more prevalent in IBD patients (19%) than in gastrointestinal-diseased controls (1.7%) (P = 0.0008) and healthy controls (5%) (P = 0.01). Anti-FAM84A antibodies were found in 26.6% of UC patients and in 11.7% of CD patients. FAM84A was confirmed as target antigen in IBD by means of Western blotting in a large independent cohort (100 UC patients, 106 CD patients, 102 healthy controls, and 100 gastrointestinal-diseased controls). Antibodies to FAM84A were significantly more prevalent in IBD patients (20%) than in gastrointestinal-diseased controls (5%) (P = 0.0004) and healthy controls (0%) (P < 0.0001). Anti-FAM84A antibodies were found in 18% of UC patients and in 22% of CD patients.
Conclusions
We identified FAM84A as a novel autoantigen in IBD. (Inflamm Bowel Dis 2011;)
Oxford University Press