Harmsen Hermie J M, Pouwels Simon D, Funke Anouk, Bos Nicolaas A, Dijkstra Gerard
Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlandsa.
Clin Vaccine Immunol. 2012 Apr;19(4):515-21. doi: 10.1128/CVI.05517-11. Epub 2012 Feb 15.
In Crohn's disease (CD), chronic gut inflammation leads to loss of mucosal barrier integrity. Subsequent leakage of IgG to the gut could produce an increase of IgG coating of intestinal bacteria. We investigated if there is more IgG coating in patients than in volunteers and whether this is dependent on the host IgG response or on the gut bacteria. Fecal and serum samples were obtained from 23 CD patients and 11 healthy volunteers. Both the in vivo IgG-coated fecal bacteria and in vitro IgG coating after serum addition were measured by flow cytometry and related to disease activity. The bacterial composition in feces was determined using fluorescence in situ hybridization. The IgG-binding capacities of Escherichia coli strains isolated from feces of patients and volunteers were assessed. The results showed that the in vivo IgG-coated fraction of fecal bacteria of patients was slightly larger than that of volunteers but significantly larger after incubation with either autologous or heterologous serum. This was dependent on the bacteria and independent of disease activity or the serum used. The presence of more Enterobacteriaceae and fewer faecalibacteria in patient feces was confirmed. E. coli isolates from patients bound more IgG than isolates from volunteers (P < 0.05) after the addition of autologous serum. Together, these results indicate that CD patients have more IgG-binding gut bacteria than healthy volunteers. We showed that the level of IgG coating depends on the bacteria and not on the serum used. Furthermore, CD patients have a strong specific immune response to their own E. coli bacteria.
在克罗恩病(CD)中,慢性肠道炎症导致黏膜屏障完整性丧失。随后,IgG渗漏至肠道可使肠道细菌的IgG包被增加。我们研究了患者的IgG包被是否比志愿者更多,以及这是否取决于宿主的IgG反应或肠道细菌。从23例CD患者和11名健康志愿者获取粪便和血清样本。通过流式细胞术检测体内IgG包被的粪便细菌以及添加血清后的体外IgG包被情况,并将其与疾病活动度相关联。使用荧光原位杂交法测定粪便中的细菌组成。评估从患者和志愿者粪便中分离出的大肠杆菌菌株的IgG结合能力。结果显示,患者粪便细菌的体内IgG包被部分略大于志愿者,但在与自体或异体血清孵育后显著增大。这取决于细菌,与疾病活动度或所用血清无关。证实患者粪便中肠杆菌科细菌较多而粪杆菌较少。添加自体血清后,从患者分离出的大肠杆菌比从志愿者分离出的大肠杆菌结合更多的IgG(P<0.05)。总之,这些结果表明,CD患者比健康志愿者有更多结合IgG的肠道细菌。我们发现IgG包被水平取决于细菌而非所用血清。此外,CD患者对自身的大肠杆菌有强烈的特异性免疫反应。