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P228. IgG4-positive plasma cells in the colon of patients with ulcerative colitis are markers of endoscopic and histological disease activity

K. Orlicka1, E.L. Culver2, A.C. Bateman3, R. Sadler4, R.W. Chapman2, S. Keshav2, E. Barnes2, S.P. Travis2, 1John Radcliffe Hospital, Translational Gastroenterology Unit, Oxford, United Kingdom, 2John Radcliffe Hospital, Translational Gastroenterology Unit and Nuffield Department of Medicine, Oxford, United Kingdom, 3Southampton General Hospital, Histopathology Department, Southampton, United Kingdom, 4Churchill Hospital, Clinical Immunology Department, Oxford, United Kingdom

Background

A lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells are key features of IgG4-related disease (IgG4-RD); a condition characterised by elevated serum IgG4, multiple organ involvement and rapid steroid response. The relevance of elevated serum IgG4 or prominent colonic IgG4-positive plasma cells in patients with ulcerative colitis (UC) is unknown.

Aims: (1) To measure serum IgG4 and tissue IgG4 in patients with UC; (2) To investigate the relationship of IgG4 with disease activity; (3) To determine if patients with UC and elevated IgG4 had IgG4-RD.

Methods

Patients with histologically confirmed UC were identified from a prospective inflammatory bowel disease serum and tissue biobank. Serum total IgG and IgG4 were measured by nephelometry in patients and 50 sex-matched healthy controls. Colonic biopsies were reviewed for disease activity and IgG4 immunostaining (mean of 3 high power fields) by a specialist histopathologist. Endoscopy reports were scored for disease activity (vascular pattern, bleeding & ulcers) by two gastroenterologists. Demographics and clinical details were collected retrospectively.

Results

54 UC patients, median age 46yrs (range 19–69yrs) and 56% female with a median UC duration of 12yrs (0–40yrs) were included. Most had left-sided disease or proctitis (67%), CRP < 0.5 mg/dL (69%) and disease remission or mild activity (93% endoscopic, 80% histological), with all on 5-ASA, 31% immunomodulators, 19% prednisolone and 4% anti-TNF. Colectomy in 6/54 (3 refractory disease, 2 dysplasia and 1 colorectal cancer). PSC in 3/54 (5.6%).

Serum IgG4 was elevated (>1.4g/L) in 3/54 (6%) patients with UC and 1/50 (2%) controls; associated with male gender (13% v 0%, p = 0.046) and PSC (33% v 4%, p = 0.031). Tissue IgG4 was elevated (>10 cells/HPF) in 22% (12/54) with UC, median 4 (0–65 cells/HPF); associated with endoscopic severity (p = 0.012) and histological activity (p = 0.001). Tissue IgG4 >20/HPF in 9.3% and >50/HPF in 1.9% of patients was associated with histological severity (p < 0.0001). Patients with elevated tissue IgG4 (>10/HPF) were more likely to require prednisolone (50% v 16%, p = 0.022) or immunomodulators (38% v 11%, p = 0.03). No patients fulfilled diagnostic criteria for IgG4-RD.

Conclusion

Elevated serum IgG4 and tissue IgG4 occurs in a minority of patients with UC in the absence of IgG4-RD. IgG4-positive plasma cells in the colon are associated with disease activity and severity. Prospective follow-up will determine if any develop IgG4-RD.