Istituto per l'Infanzia Burlo Garofolo, Via dell'Istria 65/1, Trieste 34100, Italy.
Gut. 2011 Nov;60(11):1487-93. doi: 10.1136/gut.2010.232900. Epub 2011 Apr 6.
Antitransglutaminase (anti-TG2) antibodies are synthesised in the intestine and their presence seems predictive of future coeliac disease (CD). This study investigates whether mucosal antibodies represent an early stage of gluten intolerance even in the absence of intestinal damage and serum anti-TG2 antibodies.
This study investigated 22 relatives of patients with CD genetically predisposed to gluten intolerance but negative for both serum anti-TG2 antibodies and intestinal abnormalities. Fifteen subjects were symptomatic and seven were asymptomatic. The presence of immunoglobulin A anti-TG2 antibodies in the intestine was studied by creating phage-antibody libraries against TG-2. The presence of intestinal anti-TG2 antibodies was compared with the serum concentration of the intestinal fatty acid-binding protein (I-FABP), a marker for early intestinal mucosal damage. The effects of a 12-month gluten-free diet on anti-TG2 antibody production and the subjects' clinical condition was monitored. Twelve subjects entered the study as controls.
The intestinal mucosa appeared normal in 18/22; 4 had a slight increase in intraepithelial lymphocytes. Mucosal anti-TG2 antibodies were isolated in 15/22 subjects (68%); in particular symptomatic subjects were positive in 13/15 cases and asymptomatic subjects in 2/7 cases (p=0.01). No mucosal antibodies were selected from the controls' biopsies. There was significant correlation between the presence of intestinal anti-TG2 antibodies and positive concentrations of I-FABP (p=0.0008). After a gluten-free diet, 19/22 subjects underwent a second intestinal biopsy, which showed that anti-TG2 antibodies had disappeared in 12/15 (p=0.002), while I-FABP decreased significantly (p<0.0001). The diet resolved both extraintestinal and intestinal symptoms.
A new form of genetic-dependent gluten intolerance has been described in which none of the usual diagnostic markers is present. Symptoms and intestinal anti-TG2 antibodies respond to a gluten free-diet. The detection of intestinal anti-TG2 antibodies by the phage-antibody libraries has an important diagnostic and therapeutic impact for the subjects with gluten-dependent intestinal or extraintestinal symptoms. Clinical trial number NCT00677495.
抗转谷氨酰胺酶（anti-TG2）抗体在肠道中合成，其存在似乎可预测未来的乳糜泻（CD）。本研究旨在调查即使在没有肠道损伤和血清抗 TG2 抗体的情况下，黏膜抗体是否代表对麸质不耐受的早期阶段。
本研究调查了 22 名 CD 患者的遗传易感性亲属，这些亲属对麸质不耐受，但血清抗 TG2 抗体和肠道异常均为阴性。15 名患者有症状，7 名无症状。通过针对 TG-2 构建噬菌体抗体文库，研究了肠道中免疫球蛋白 A 型抗 TG2 抗体的存在。将肠道抗 TG2 抗体的存在与肠道脂肪酸结合蛋白（I-FABP）的血清浓度进行比较，I-FABP 是早期肠道黏膜损伤的标志物。监测了 12 个月无麸质饮食对抗 TG2 抗体产生和患者临床状况的影响。12 名患者作为对照组进入研究。
22 名患者中，18 名患者的肠道黏膜外观正常，4 名患者上皮内淋巴细胞略有增加。15/22 名患者（68%）分离出黏膜抗 TG2 抗体，特别是有症状的患者 13/15 例阳性，无症状的患者 2/7 例阳性（p=0.01）。对照组活检未选择黏膜抗体。肠道抗 TG2 抗体的存在与 I-FABP 阳性浓度显著相关（p=0.0008）。无麸质饮食后，22 名患者中的 19 名接受了第二次肠道活检，结果显示 15 名患者中的 12 名（p=0.002）抗 TG2 抗体消失，而 I-FABP 显著降低（p<0.0001）。饮食解决了肠内和肠外症状。
描述了一种新的遗传依赖性麸质不耐受形式，其中没有任何常用的诊断标志物存在。症状和肠道抗 TG2 抗体对无麸质饮食有反应。通过噬菌体抗体文库检测肠道抗 TG2 抗体对有肠内或肠外症状的患者具有重要的诊断和治疗意义。临床试验注册号 NCT00677495。
