Peracchi Maddalena, Trovato Cristina, Longhi Massimo, Gasparin Maurizio, Conte Dario, Tarantino Cristina, Prati Daniele, Bardella Maria Teresa
IRCCS-Ospedale Maggiore, University of Milan, Italy.
Am J Gastroenterol. 2002 Nov;97(11):2850-4. doi: 10.1111/j.1572-0241.2002.07033.x.
For celiac disease (CD), screening a trend has recently emerged to measure tissue transglutaminase antibodies (tTGA) by immunoassays instead of the more laborious endomysial antibodies (EmA), as they recognize the same target, tissue transglutaminase (tTG). However, a high rate of false-positive results has been reported in some patient series with diseases known to be associated with CD. Moreover, tTG is a ubiquitous, multifunctional enzyme, overexpressed in experimental models of heart failure. Therefore, we assessed the specificity of tTGA assays in a large series of EmA-negative patients with end-stage heart failure.
We studied 288 patients with end-stage heart failure and 60 blood donors. No subject had clinical evidence of CD or IgA deficiency, and all were EmA negative. Serum IgA and IgG tTGA were measured by means of commercial kits using as substrate, either guinea pig or recombinant human tTG. Blocking studies and Western blots were also performed using recombinant human tTG.
All blood donor sera were IgA tTGA negative. IgA tTGA positivity was observed in 47.6% and 49.1% of patients with heart failure using, respectively, guinea pig tTG and recombinant human tTG as substrates. Preincubation of positive sera with recombinant human tTG resulted in 81% blocking of IgA tTGA in immunoassay. Western blot analysis confirmed the presence of antibodies against recombinant human tTG. IgA tTGA-positive sera were also IgG tTGA positive.
IgA and IgG tTGA occur in a large number of EmA-negative patients with end-stage heart failure, and their presence is unlikely to be caused by concomitant CD.
对于乳糜泻（CD），最近出现了一种筛查趋势，即通过免疫测定法检测组织转谷氨酰胺酶抗体（tTGA），而不是采用更为繁琐的肌内膜抗体（EmA），因为它们识别相同的靶标——组织转谷氨酰胺酶（tTG）。然而，在一些已知与CD相关疾病的患者系列中，已报道了较高的假阳性结果率。此外，tTG是一种普遍存在的多功能酶，在心力衰竭的实验模型中过度表达。因此，我们在一大系列EmA阴性的终末期心力衰竭患者中评估了tTGA检测的特异性。
我们研究了288例终末期心力衰竭患者和60名献血者。所有受试者均无CD或IgA缺乏的临床证据，且EmA均为阴性。使用商业试剂盒，以豚鼠或重组人tTG作为底物，检测血清IgA和IgG tTGA。还使用重组人tTG进行了阻断研究和蛋白质印迹分析。
所有献血者血清的IgA tTGA均为阴性。分别以豚鼠tTG和重组人tTG作为底物时，在47.6%和49.1%的心力衰竭患者中观察到IgA tTGA阳性。阳性血清与重组人tTG预温育导致免疫测定中IgA tTGA的81%被阻断。蛋白质印迹分析证实存在针对重组人tTG的抗体。IgA tTGA阳性血清的IgG tTGA也呈阳性。
IgA和IgG tTGA在大量EmA阴性的终末期心力衰竭患者中出现，其存在不太可能由合并的CD引起。
