Tissue IgG4-positive plasma cells in inflammatory bowel disease: a study of 88 treatment-naive biopsies of inflammatory bowel disease.
The distinction of Crohn's disease from ulcerative colitis is based on clinical, endoscopic, radiological, and histological findings, a paradigm that remains unchanged despite the advent of new understanding of the immunological and genetic basis of inflammatory bowel disease. There is a strong correlation between inflammatory bowel disease, predominantly ulcerative colitis, and autoimmune pancreatitis. We hypothesized that colonic biopsies from patients with inflammatory bowel disease would demonstrate increased numbers of IgG4-positive plasma cells and that this elevation might be restricted to ulcerative colitis. We examined a cohort of 78 cases of inflammatory bowel disease: 50 ulcerative colitis and 38 Crohn's disease. We identified treatment-naive biopsies. Additionally, four cases of inflammatory bowel disease associated with autoimmune pancreatitis and 15 cases of lymphocytic/collagenous colitis were also identified. Immunohistochemical stains for IgG4 were performed. Biopsies from patients with ulcerative colitis showed significantly higher numbers of IgG4-bearing plasma cells than those with Crohn's disease (mean IgG4 counts per high-power field (hpf) 9.8 vs 2.8, P=0.001). Samples from 19 (38%) ulcerative colitis patients had IgG4 counts >10/hpf, compared with only two (5%) patients with Crohn's disease; the sensitivity and specificity of a cutoff at 10 IgG4-positive plasma cells per hpf was 38 and 95%, respectively. Among individuals <18 years, there were no statistically differences in the IgG4 counts between the two subforms of inflammatory bowel disease. Among adult patients, a cutoff of 5 IgG4+ plasma cells distinguished ulcerative colitis from Crohn's disease with a sensitivity of 53% and specificity of 83%. In comparison to inflammatory bowel disease, patients with lymphocytic/collagenous colitis showed significantly lower numbers of IgG4-positive plasma cells (P=0.0001). Ulcerative colitis with pancolitis showed higher numbers of IgG4-bearing plasma cells (mean IgG4 12.8 vs 5.8 per hpf; P=0.09). An immunohistochemical stain for IgG4 may aid in making the distinction between ulcerative colitis and Crohn's disease (with exclusion of the pediatric cases), albeit with a relatively low sensitivity. This study also provides additional support to the hypothesis that a subset of ulcerative colitis cases is associated with a Th2 response.
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Renu
R
Virk
Department of Pathology, Tufts Medical Center, Boston, MA, USA.
Shweta
S
Shinagare
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Gregory Y
GY
Lauwers
Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Vijay
V
Yajnik
Department of Medicine, Division of Rheumatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
John H
JH
Stone
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Vikram
V
Deshpande
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000276:immunology*; D003424:Crohn Disease / Q000175:diagnosis* / Q000276:immunology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology*; D055815:Young Adult
D007074:Immunoglobulin G