Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Department of Pathology, Tufts Medical Center, Boston, MA, USA.
Mod Pathol. 2014 Mar;27(3):454-9. doi: 10.1038/modpathol.2013.121. Epub 2013 Aug 9.
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.
克罗恩病和溃疡性结肠炎的鉴别基于临床、内镜、影像学和组织学发现，尽管对炎症性肠病的免疫学和遗传学基础有了新的认识，但这一范式仍然没有改变。炎症性肠病（主要是溃疡性结肠炎）和自身免疫性胰腺炎之间存在很强的相关性。我们假设炎症性肠病患者的结肠活检会显示出更多的 IgG4 阳性浆细胞，并且这种升高可能仅限于溃疡性结肠炎。我们检查了一组 78 例炎症性肠病病例：50 例溃疡性结肠炎和 38 例克罗恩病。我们确定了未经治疗的活检。此外，还发现了 4 例与自身免疫性胰腺炎相关的炎症性肠病病例和 15 例淋巴细胞/胶原性结肠炎病例。进行了 IgG4 的免疫组织化学染色。溃疡性结肠炎患者的活检显示 IgG4 阳性浆细胞的数量明显高于克罗恩病患者（高倍镜视野下 IgG4 计数中位数分别为 9.8 和 2.8，P=0.001）。19 例（38%）溃疡性结肠炎患者的 IgG4 计数>10/hpf，而克罗恩病患者只有 2 例（5%）；10 个 IgG4 阳性浆细胞/hpf 的截断值的敏感性和特异性分别为 38%和 95%。在<18 岁的人群中，两种炎症性肠病亚型之间的 IgG4 计数没有统计学差异。在成年患者中，5 IgG4+浆细胞的截断值可将溃疡性结肠炎与克罗恩病区分开来，其敏感性为 53%，特异性为 83%。与炎症性肠病相比，淋巴细胞/胶原性结肠炎患者的 IgG4 阳性浆细胞数量明显较少（P=0.0001）。全结肠炎的溃疡性结肠炎患者 IgG4 阳性浆细胞较多（平均 IgG4 计数分别为 12.8 和 5.8/hpf；P=0.09）。IgG4 的免疫组织化学染色可能有助于区分溃疡性结肠炎和克罗恩病（排除儿科病例），尽管敏感性相对较低。这项研究还为溃疡性结肠炎的一个亚组与 Th2 反应相关的假设提供了更多支持。
