Lock R J, Gilmour J E, Unsworth D J
Immunology Department, Southmead Hospital, International Blood Group Reference Laboratory, Bristol, UK.
Clin Exp Immunol. 1999 May;116(2):258-62. doi: 10.1046/j.1365-2249.1999.00909.x.
Anti-tissue transglutaminase has been recently described as the predominant autoantigen in coeliac disease. We purified serum anti-tissue transglutaminase antibodies from three patients with coeliac disease by column chromatography and eluted tissue section-bound R1-anti-reticulin antibodies from sections of rat tissue for two of these. Lastly, we generated seven mouse MoAbs to guinea pig tissue transglutaminase. Each preparation was examined for anti-tissue transglutaminase, anti-endomysium, anti-R1 reticulin and anti-gliadin antibodies. Column-purified patient antibodies and 2/7 mouse MoAbs gave characteristic anti-endomysium/anti-R1 reticulin reactivity on rat, monkey and human tissue. All positive sera gave indistinguishable patterns of immunofluorescence on rat liver, kidney and stomach, monkey oesophagus, and human umbilical cord. Anti-R1-reticulin eluted from sections showed anti-tissue transglutaminase reactivity in 2/2 cases, but 0/2 showed anti-gliadin reactivity. In both, tissue section-eluted anti-R1 reticulin gave endomysial staining on monkey oesophagus. None of the mouse monoclonals, or any of the purified patient's anti-tissue transglutaminase or anti-R1-reticulin antibody showed any reactivity with gliadin. These data confirm tissue transglutaminase as the predominant autoantigen in coeliac disease and suggest that both anti-endomysium and anti-R1 reticulin reactivities seen in coeliac disease arise due to an immune response to tissue transglutaminase. Rigorous immunoabsorption was sufficient to abrogate reactivity in the tissue transglutaminase ELISA, but failed to completely absorb anti-endomysium and anti-reticulin activity. The possibility remains that some of the anti-endomysium and anti-reticulin activity was directed against antigens other than tissue transglutaminase.
抗组织转谷氨酰胺酶最近被描述为乳糜泻中的主要自身抗原。我们通过柱色谱法从三名乳糜泻患者中纯化血清抗组织转谷氨酰胺酶抗体，并从其中两名患者的大鼠组织切片中洗脱与组织切片结合的R1抗网硬蛋白抗体。最后，我们制备了7种针对豚鼠组织转谷氨酰胺酶的小鼠单克隆抗体。对每种制剂检测其抗组织转谷氨酰胺酶、抗肌内膜、抗R1网硬蛋白和抗麦醇溶蛋白抗体。柱纯化的患者抗体和7种小鼠单克隆抗体中的2种在大鼠、猴和人组织上呈现出特征性的抗肌内膜/抗R1网硬蛋白反应性。所有阳性血清在大鼠肝脏、肾脏和胃、猴食管以及人脐带上呈现出难以区分的免疫荧光模式。从切片中洗脱的抗R1网硬蛋白在2/2的病例中显示出抗组织转谷氨酰胺酶反应性，但0/2显示出抗麦醇溶蛋白反应性。在这两种情况下，从组织切片洗脱的抗R1网硬蛋白在猴食管上呈现出肌内膜染色。没有一种小鼠单克隆抗体，或任何纯化的患者抗组织转谷氨酰胺酶或抗R1网硬蛋白抗体与麦醇溶蛋白显示出任何反应性。这些数据证实组织转谷氨酰胺酶是乳糜泻中的主要自身抗原，并表明乳糜泻中所见的抗肌内膜和抗R1网硬蛋白反应性均源于对组织转谷氨酰胺酶的免疫反应。严格的免疫吸附足以消除组织转谷氨酰胺酶ELISA中的反应性，但未能完全吸收抗肌内膜和抗网硬蛋白活性。抗肌内膜和抗网硬蛋白活性的一部分可能针对组织转谷氨酰胺酶以外的抗原，这种可能性仍然存在。
