Department of Pediatrics, San Raffaele Scientific Institute, Via Olgettina 60, Milan 20132, Italy.
Ital J Pediatr. 2010 Mar 18;36:25. doi: 10.1186/1824-7288-36-25.
Previous studies have demonstrated that the presence of serum IgA antibodies against actin filaments (AAA) in patients with celiac disease (CD) is strongly associated with mucosal damage and severe degrees of villous atrophy.The aims of the present study were (1) to verify the effectiveness of IgA-AAA in newly diagnosed CD patients in a clinical setting (2) to compare the immunofluorescence assay with ELISA assay; (3) to compare the correlation of our IgA anti-tissue transglutaminase antibodies (tTG-Ab) class with mucosal intestinal lesions.
90 patients underwent endoscopy and multiple biopsies for suspected CD on the basis of symptoms, in presence of positive tTG-Ab tests. Twenty biopsied and 25 not-biopsied subjects with negative tTG-Ab were tested as control groups. IgA-AAA assays were performed by indirect immunofluorescence using rat epithelial intestinal cells, and by ELISA with a commercial kit. tTG-Ab assay was a radio-binding assay. Intestinal specimens were collected by upper endoscopy and the histological study was done according to the Marsh's classification modified by Oberhuber (M/O). Auto-antibodies assays and histological evaluation have been performed blindly by skilled operators.
CD diagnosis was confirmed in 82 patients (type I M/O in 2 patients, IIIA in 18 patients, IIIB in 29 patients and IIIC in 33 patients). Two patients with type 1 lesion in presence of positive tTG-Ab and abdominal complaints, started a gluten free diet. The rate of IgA-AAA positivity (sensitivity) by IFI and ELISA in histologically proven celiac disease patients, were 5.5% and 25% patients in IIIA, 27.5% and 34.4% patients in IIIB, 78.8% and 75% in IIIC patients, respectively.Patients with normal or nearly normal mucosa, regardless of tTG-Ab status, presented negative IgA-AAA IFI assay. On the other hand, 1 patient with normal mucosa but positive tTG-Ab, also presented positive IgA-AAA ELISA. All healthy non biopsied controls had negative IgA-AAA. tTG-Ab serum concentration was significantly correlated with more severe intestinal lesion (IIIB, IIIC M/O).
IgA-AAA may be undetectable in presence of severe mucosal damage. Histology is still necessary to diagnose celiac disease and IgA-AAA cannot be included in usual screening tests, because it has little to offer if compared to the well-established tTG-Ab.IgA-AAA could be an adjunctive, very useful tool to support the diagnosis of CD in case of suboptimal histology, when the biopsy is to be avoided for clinical reasons, or in case of negative parents' consensus.
先前的研究表明,乳糜泻(CD)患者血清中针对肌动蛋白丝的 IgA 抗体(AAA)的存在与黏膜损伤和严重程度的绒毛萎缩密切相关。本研究的目的是:(1)在临床环境中验证新诊断的 CD 患者中 IgA-AAA 的有效性;(2)比较免疫荧光法和 ELISA 法;(3)比较我们的 IgA 抗组织转谷氨酰胺酶抗体(tTG-Ab)与黏膜肠内病变的相关性。
90 例疑似 CD 患者因症状而行内镜和多次活检,同时进行 tTG-Ab 检测。20 例活检和 25 例未活检的 tTG-Ab 阴性患者作为对照组。使用大鼠肠上皮细胞间接免疫荧光法和商业试剂盒进行 IgA-AAA 检测。tTG-Ab 检测采用放射性结合测定法。通过上消化道内镜收集肠标本,并根据 Oberhuber 改良的 Marsh 分类(M/O)进行组织学研究。由熟练的操作人员进行自身抗体检测和组织学评估。
82 例患者确诊为 CD(2 例为 1 型 M/O,18 例为 3A 型,29 例为 3B 型,33 例为 3C 型)。2 例有阳性 tTG-Ab 和腹部不适的 1 型病变患者开始无麸质饮食。组织学证实的乳糜泻患者中,IFI 和 ELISA 检测的 IgA-AAA 阳性率(敏感性)分别为 5.5%和 25%的 3A 型患者,27.5%和 34.4%的 3B 型患者,78.8%和 75%的 3C 型患者。无论 tTG-Ab 状态如何,正常或几乎正常黏膜的患者均呈现 IFI 检测的 IgA-AAA 阴性。另一方面,1 例黏膜正常但 tTG-Ab 阳性的患者,也呈现 IgA-AAA ELISA 阳性。所有健康非活检对照者的 IgA-AAA 均为阴性。tTG-Ab 血清浓度与更严重的肠损伤(3B 型、3C 型 M/O)显著相关。
在严重黏膜损伤的情况下,IgA-AAA 可能无法检测到。组织学仍然是诊断乳糜泻所必需的,并且 IgA-AAA 不能被纳入常规筛查试验,因为与已经确立的 tTG-Ab 相比,它提供的信息很少。在组织学不理想的情况下,为避免临床原因进行活检,或在父母不同意的情况下,IgA-AAA 可能是一种有用的辅助诊断工具,有助于支持 CD 的诊断。