Frehn Lisa, Jansen Anke, Bennek Eveline, Mandic Ana D, Temizel Ilknur, Tischendorf Stefanie, Verdier Julien, Tacke Frank, Streetz Konrad, Trautwein Christian, Sellge Gernot
Department of Internal Medicine III, University Hospital Aachen, RWTH University, Aachen, Germany.
PLoS One. 2014 Sep 12;9(9):e106750. doi: 10.1371/journal.pone.0106750. eCollection 2014.
Inflammatory bowel disease (IBD) is associated with a defective intestinal barrier and enhanced adaptive immune responses against commensal microbiota. Immune responses against food antigens in IBD patients remain poorly defined.
IgG and IgA specific for food and microfloral antigens (wheat and milk extracts; purified ovalbumin; Escherichia coli and Bacteroides fragilis lysates; mannan from Saccharomyces cerevisiae) were analyzed by ELISA in the serum and feces of patients with Crohn's disease (CD; n = 52 for serum and n = 20 for feces), ulcerative colitis (UC; n = 29; n = 17), acute gastroenteritis/colitis (AGE; n = 12; n = 9) as well as non-inflammatory controls (n = 61; n = 39).
Serum anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-B. fragilis IgG and IgA levels were increased in CD patients whereas antibody (Ab) levels against E. coli and food antigens were not significantly different within the patient groups and controls. Subgroup analysis revealed that CD patients with severe diseases defined by stricturing and penetrating lesions have slightly higher anti-food and anti-microbial IgA levels whereas CD and UC patients with arthropathy have decreased anti-food IgG levels. Treatment with anti-TNF-α Abs in CD patients was associated with significantly decreased ASCA IgG and IgA and anti-E. coli IgG. In the feces specific IgG levels against all antigens were higher in CD and AGE patients while specific IgA levels were higher in non-IBD patients. Anti-food IgG and IgA levels did not correlate with food intolerance.
In contrast to anti-microbial Abs, we found only minor changes in serum anti-food Ab levels in specific subgroups of IBD patients. Fecal Ab levels towards microbial and food antigens show distinct patterns in controls, CD and UC patients.
炎症性肠病(IBD)与肠道屏障缺陷及针对共生微生物群的适应性免疫反应增强有关。IBD患者针对食物抗原的免疫反应仍未明确。
采用酶联免疫吸附测定(ELISA)法分析克罗恩病(CD;血清n = 52,粪便n = 20)、溃疡性结肠炎(UC;n = 29;n = 17)、急性胃肠炎/结肠炎(AGE;n = 12;n = 9)患者以及非炎症对照组(n = 61;n = 39)血清和粪便中针对食物和微生物抗原(小麦和牛奶提取物;纯化卵清蛋白;大肠杆菌和脆弱拟杆菌裂解物;酿酒酵母甘露聚糖)的IgG和IgA。
CD患者血清中抗酿酒酵母抗体(ASCA)以及抗脆弱拟杆菌IgG和IgA水平升高,而患者组和对照组中针对大肠杆菌和食物抗原的抗体(Ab)水平无显著差异。亚组分析显示,由狭窄和穿透性病变定义的重症CD患者抗食物和抗微生物IgA水平略高,而患有关节病的CD和UC患者抗食物IgG水平降低。CD患者接受抗TNF-α抗体治疗后,ASCA IgG和IgA以及抗大肠杆菌IgG显著降低。在粪便中,CD和AGE患者针对所有抗原的特异性IgG水平较高,而非IBD患者的特异性IgA水平较高。抗食物IgG和IgA水平与食物不耐受无关。
与抗微生物抗体不同,我们发现IBD患者特定亚组的血清抗食物抗体水平仅有微小变化。对照组、CD和UC患者粪便中针对微生物和食物抗原的抗体水平呈现不同模式。