Arsenescu R, Bruno M E C, Rogier E W, Stefka A T, McMahan A E, Wright T B, Nasser M S, de Villiers W J S, Kaetzel C S
Division of Digestive Diseases & Nutrition, Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Mucosal Immunol. 2008 Sep;1(5):399-411. doi: 10.1038/mi.2008.32. Epub 2008 Jul 2.
In an effort to develop a molecular classification scheme for Crohn's disease (CD), mucosal biopsies from 69 CD patients and 28 normal controls were analyzed for expression of the RelA subunit of nuclear factor (NF)-kappaB, A20 (a negative regulator of NF-kappaB), polymeric immunoglobulin receptor (pIgR), tumor necrosis factor (TNF), and interleukin (IL)-8. Principal component analysis was used to classify individuals into three subsets based on patterns of biomarker expression. Set 1 included normal subjects and CD patients with mild disease and good responses to therapy, thus defining "normal" biomarker expression. CD patients in set 2, characterized by low expression of all five biomarkers, had moderate to severe disease and poor responses to immunosuppressive and anti-TNF therapy. Patients in set 3, characterized by low expression of RelA, A20, and pIgR, normal TNF and elevated IL-8, had acute inflammation that responded well to therapy. Classification of CD patients by these biomarkers may predict disease behavior and responses to therapy.
为了制定克罗恩病（CD）的分子分类方案，对69例CD患者和28例正常对照的黏膜活检组织进行分析，检测核因子（NF）-κB的RelA亚基、A20（NF-κB的负调节因子）、多聚免疫球蛋白受体（pIgR）、肿瘤坏死因子（TNF）和白细胞介素（IL）-8的表达。采用主成分分析，根据生物标志物表达模式将个体分为三个亚组。第1组包括正常受试者和病情较轻且对治疗反应良好的CD患者，从而定义了“正常”生物标志物表达。第2组的CD患者所有5种生物标志物表达均较低，患有中度至重度疾病，对免疫抑制和抗TNF治疗反应不佳。第3组患者的特征是RelA、A20和pIgR表达较低，TNF正常而IL-8升高，患有对治疗反应良好的急性炎症。通过这些生物标志物对CD患者进行分类可能预测疾病行为和治疗反应。
