[719] The Significance of IGG4 in Inflammatory Bowel Disease.

Renu K Virk, Gregory Y Lauwers, Vikram Deshpande. UMass Memorial Medical Center, Worcester, MA; Massachusetts General Hospital, Boston

Background: IgG4 has emerged as a diagnostic marker for autoimmune pancreatitis (AIP). Several prior studies have noted an elevated risk of inflammatory bowel disease (IBD) in patients with AIP, and the majority of these patients have ulcerative colitis (UC). Based on this data, and the observations that both UC and AIP show robust Th2 type responses, we hypothesized that IgG4 stain may assist in distinguishing UC from Crohn's disease (CD), the latter being associated with a Th1/Th17 CD4 response.
Design: We evaluated consecutive patients with UC (n= 42), and CD (n=34). The biopsies we evaluated were obtained at their initial presentation and prior to therapy. The median follow-up of this cohort was 52 months. Four cases of AIP with IBD were also evaluated, as were 16 cases of lymphocytic/collagenous (microscopic colitis, MC). The inflammatory activity in these biopsies was graded as 1 (cryptitis only), 2 (crypt abscesses), and 3 (ulceration). IgG4 and IgG immunostains were performed. A single high power field (HPF) with the highest number of IgG4 positive plasma cells was enumerated. The same HPF was located on the IgG stain and the number of immunoreactive plasma cells counted.
Results: UC cases showed significantly more IgG4 positive plasma cells than CD (p<0.0001) and also showed higher IgG4 to IgG ratio (p=0.001).

IgG4 in inflammatory bowel disease

Disease	Mean IgG4/HPF (median/SD)	Mean IgG4/IgG ratio
Ulcerative colitis	10.6 (6/13)	0.2
Crohn's disease	2.1 (1/2.7)	0.06

At a cut point of 5 IgG4 positive plasma cells, this stain distinguished UC from CD with a specificity of 87% and sensitivity of 54%. Within the UC cohort, patients with pancolitis showed higher IgG4 counts than cases without pancolitis (mean 13 vs. 6; p=0.05). Interestingly, UC cases whose biopsies showed >5 IgG4 positive cells were significantly more likely to be associated with grade 3 inflammatory activity (p=0.01). All 4 AIP cases with IBD showed IgG4 positive cells (mean 9) in their colonic biopsies. Cases of microscopic colitis showed significantly fewer IgG4 positive cells than UC (p=0.0001), but similar number of these cells as CD (p=0.37).
Conclusions: IgG4 shows promise as a biomarker in distinguishing UC from CD, albeit with a low sensitivity, and in the rare instances of overlap between microscopic and ulcerative colitis. It's significance as a marker of severe disease requires further study.
Category: Gastrointestinal

Monday, February 28, 2011 11:30 AM

Platform Session: Section E, Monday Morning