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Mucosal IgG4 Cell Infiltration in Ulcerative Colitis Is Linked to Disease Activity and Primary Sclerosing Cholangitis

Raina, Amit MD, CNSC*; Yadav, Dhiraj MD, MPH*; Regueiro, Miguel MD*; Krasinskas, Alyssa M. MD; Saul, Melissa I. MS; Sapienza, Dee Ann M.; Binion, David G. MD*; Hartman, Douglas J. MD

doi: 10.1097/MIB.0b013e318281344d
Original Basic Science Article

Background: The distribution of IgG4 plasma cells in colonic mucosa, its significance, and relation to disease activity in patients with inflammatory bowel disease (IBD) is unclear. We systematically evaluated IgG4 cell distribution in colonic mucosal biopsies of patients with IBD and correlated histological findings with disease pattern and mucosal inflammation.

Methods: We reviewed clinical records and pathology specimens of 54 randomly selected patients with IBD (13 Crohn's colitis: 7 active, 6 inactive; 18 ulcerative colitis [UC]: 10 active, 8 inactive; 23 UC with primary sclerosing cholangitis: 11 active colitis, 12 inactive colitis), and 11 controls (3 nonspecific diarrhea, 8 collagenous/lymphocytic colitis) who had colonoscopy and biopsies performed at our institution from April 2003 to July 2010. Immunostains for IgG4 were performed on archived rectal biopsies. Presence of >10 IgG4 cells per high-power field (×40 field) on microscopic evaluation was considered significant.

Results: Overall, significant IgG4 plasma cell infiltration was seen in 24% of patients compared with none of the controls (P = 0.05). Within IBD groups, significant infiltration was limited to patients with UC with active colitis (30%), primary sclerosing cholangitis with inactive (25%) and active (64%) colitis. In contrast, patients with Crohn's colitis, UC with inactive colitis, and controls had rare IgG4 plasma cells. No correlation was observed between the number of IgG4 cells and degree of active inflammation. In 4 patients with UC and primary sclerosing cholangitis who had more than 1 colonoscopy and biopsies, the number of IgG4 cells fluctuated without correlation with colonic disease activity.

Conclusions: IgG4 plasma cells are significantly increased in a subset of patients with IBD suggesting the possibility of a B-cell–mediated mechanism in these patients.

Article first published online 9 April 2013

*Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania.

Reprints: Dhiraj Yadav, MD, MPH, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA 15213 (e-mail:

D. Yadav and D. J. Hartman codirected this project.

The authors have no conflicts of interest to disclose.

Received August 21, 2012

Accepted September 6, 2012

© Crohn's & Colitis Foundation of America, Inc.
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