Ashorn Sara, Raukola Hanna, Välineva Tuuli, Ashorn Merja, Wei Bo, Braun Jonathan, Rantala Immo, Kaukinen Katri, Luukkaala Tiina, Collin Pekka, Mäki Markku, Iltanen Sari
Paediatric Research Centre and Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland.
J Clin Immunol. 2008 Sep;28(5):486-94. doi: 10.1007/s10875-008-9200-9. Epub 2008 May 22.
Expression of anti-Saccharomyces cerevisiae antibodies (ASCA) identifies patients and individuals at risk for Crohn's disease and has also been reported in 40-60% of celiac disease (CD) cases, suggesting a role of host response to enteric microbiota in the development of inflammatory lesions. In this prospective study in patients with suspicion of CD, we evaluate the frequency and association of ASCA to serological responses for other host microbial targets formally associated with Crohn's disease, including the Pseudomonas fluorescens associated sequence I2 and a Bacteroides caccae TonB-linked outer membrane protein, OmpW.
Small bowel mucosal biopsies were taken from 242 patients with suspicion of CD, their sera were tested for antibodies to tissue transglutaminase (tTG), ASCA, I2, and OmpW. Eighty adult healthy blood donors were used as controls.
The diagnosis of CD was confirmed on biopsy in 134 cases. The occurrence of ASCA and I2 positivity was significantly higher in adult CD patients than in patients with non-CD disease. Anti-I2 levels in the sera were significantly higher in adult CD patients than in non-CD disease or the controls and anti-OmpW levels in CD and non-CD patients when compared to controls. Positive seroreactivity to OmpW seemed to increase with age. Of the CD patients, 90% were seropositive for at least one microbial antigen tested.
This study demonstrates a mosaic of disease-related serological responses to microbial antigens in patients with CD. Immune responses to commensal enteric bacteria may play a role in the small intestine mucosal damage in CD.
抗酿酒酵母抗体(ASCA)的表达可识别克罗恩病患者及有患病风险的个体,且在40%-60%的乳糜泻(CD)病例中也有报道,这表明宿主对肠道微生物群的反应在炎症性病变发展中起作用。在这项针对疑似克罗恩病患者的前瞻性研究中,我们评估了ASCA与其他与克罗恩病正式相关的宿主微生物靶点的血清学反应的频率及关联性,这些靶点包括荧光假单胞菌相关序列I2和粪拟杆菌TonB连接外膜蛋白OmpW。
对242例疑似克罗恩病患者进行小肠黏膜活检,检测其血清中的抗组织转谷氨酰胺酶(tTG)抗体、ASCA、I2和OmpW抗体。80名成年健康献血者作为对照。
134例经活检确诊为克罗恩病。成年克罗恩病患者中ASCA和I2阳性的发生率显著高于非克罗恩病患者。成年克罗恩病患者血清中的抗I2水平显著高于非克罗恩病患者或对照组,与对照组相比,克罗恩病患者和非克罗恩病患者血清中的抗OmpW水平也较高。对OmpW的阳性血清反应性似乎随年龄增加。在克罗恩病患者中,90%对至少一种检测的微生物抗原有血清阳性反应。
本研究表明克罗恩病患者对微生物抗原存在一系列与疾病相关的血清学反应。对共生肠道细菌的免疫反应可能在克罗恩病的小肠黏膜损伤中起作用。