Ashorn Sara, Välineva Tuuli, Kaukinen Katri, Ashorn Merja, Braun Jonathan, Raukola Hanna, Rantala Immo, Collin Pekka, Mäki Markku, Luukkaala Tiina, Iltanen Sari
Paediatric Research Centre and Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland.
J Clin Immunol. 2009 Mar;29(2):190-5. doi: 10.1007/s10875-008-9255-7. Epub 2008 Nov 6.
Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG) are commonly used for screening and diagnosing of celiac disease (CD). Seroreactivity for anti-Saccharomyces cerevisiae antibody (ASCA) and bacterial antigens have also been detected in CD patients. The aim of this study was to examine prospectively serologic responses to microbial targets in adult CD patients at the time of diagnosis and during a gluten-free diet (GFD). Further, we wanted to evaluate whether these serologic specificities could provide new tools for the follow-up of CD patients.
Data on 55 adult biopsy-proven CD patients were available for follow-up study. Upper gastrointestinal endoscopy was performed on all patients. Sera from patients were tested for antibodies to tTG and ASCA and additionally analyzed with IgA enzyme-linked immunosorbent assays to Pseudomonas fluorescens-associated sequence, I2, and to a Bacteroides caccae TonB-linked outer membrane protein, OmpW.
At the time of diagnosis, 91% of CD cases were positive for tTG and 49% for ASCA; positive seroreactivity to I2 was found in 86% and to OmpW in 60% of CD patients at the time of diagnosis. The frequency of seropositivity and serum levels of these antibodies decreased during GFD. Moreover, we found that the decline in the serum levels was significant in all of these markers (p < 0.005). Interestingly, we also found that serum levels of ASCA correlated with the grade of mucosal morphology (p = 0.021), as the ASCA serum levels declined in accordance with mucosal healing.
Commensal enteric bacteria seem to play a role in the small intestinal mucosal damage in CD. This was proven by the serological responses to different microbial antigens shown in this study. Serum levels of ASCA, anti-I2, and anti-OmpW antibodies decreased significantly during GFD, indicating that these serologic markers are gluten dependent in CD patients. These specificities could provide new tools in the follow-up of CD patients.
抗组织转谷氨酰胺酶(tTG)的免疫球蛋白A(IgA)自身抗体常用于乳糜泻(CD)的筛查和诊断。在CD患者中也检测到了抗酿酒酵母抗体(ASCA)和细菌抗原的血清反应性。本研究的目的是前瞻性地检查成年CD患者在诊断时和无麸质饮食(GFD)期间对微生物靶点的血清学反应。此外,我们想评估这些血清学特异性是否可为CD患者的随访提供新工具。
55例经活检证实的成年CD患者的数据可用于随访研究。对所有患者进行了上消化道内镜检查。检测患者血清中的tTG和ASCA抗体,并另外用IgA酶联免疫吸附试验分析针对荧光假单胞菌相关序列I2和脆弱拟杆菌TonB连接外膜蛋白OmpW的抗体。
诊断时,91%的CD病例tTG呈阳性,49%的病例ASCA呈阳性;诊断时,86%的CD患者对I2血清反应阳性,60%的患者对OmpW血清反应阳性。在GFD期间,这些抗体的血清阳性频率和血清水平下降。此外,我们发现所有这些标志物的血清水平下降均具有显著性(p < 0.005)。有趣的是,我们还发现ASCA的血清水平与黏膜形态分级相关(p = 0.021),因为ASCA血清水平随着黏膜愈合而下降。
共生肠道细菌似乎在CD的小肠黏膜损伤中起作用。本研究中对不同微生物抗原的血清学反应证明了这一点。在GFD期间,ASCA、抗I2和抗OmpW抗体的血清水平显著下降,表明这些血清学标志物在CD患者中依赖于麸质。这些特异性可为CD患者的随访提供新工具。