Marzari R, Sblattero D, Florian F, Tongiorgi E, Not T, Tommasini A, Ventura A, Bradbury A
Dipartimento di Biologia, Università di Trieste, Trieste, Italy.
J Immunol. 2001 Mar 15;166(6):4170-6. doi: 10.4049/jimmunol.166.6.4170.
Celiac disease (CD) is an intestinal malabsorption characterized by intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and tissue transglutaminase, an autoantigen located in the endomysium. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. The role of gliadins in eliciting the immune response in CD and how transglutaminase is linked to the primary reaction are still unclear. In this work, we report the production and analysis of six phage Ab libraries from the peripheral and intestinal lymphocytes of three CD patients. We were able to isolate Abs to transglutaminase from all intestinal lymphocytes libraries but not from those obtained from peripheral lymphocytes. This is in contrast to Abs against gliadin, which could be obtained from all libraries, indicating that the humoral response against transglutaminase occurs at the local level, whereas that against gliadin occurs both peripherally and centrally. Abs from all three patients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family. The possible role of these anti-transglutaminase Abs in the onset of CD and associated autoimmune pathologies is discussed.
乳糜泻（CD）是一种肠道吸收不良疾病，其特征为对谷物蛋白不耐受，并伴有对膳食麦醇溶蛋白和组织转谷氨酰胺酶（一种位于肌内膜的自身抗原）的免疫反应。组织转谷氨酰胺酶属于催化蛋白质交联反应的酶家族，在许多组织中组成性表达，并在细胞凋亡过程中被激活。麦醇溶蛋白在引发CD免疫反应中的作用以及转谷氨酰胺酶如何与初级反应相关联仍不清楚。在这项工作中，我们报告了从三名CD患者的外周血和肠道淋巴细胞中制备和分析六个噬菌体抗体文库的情况。我们能够从所有肠道淋巴细胞文库中分离出针对转谷氨酰胺酶的抗体，但从外周淋巴细胞获得的文库中却未能分离出。这与针对麦醇溶蛋白的抗体形成对比，后者可从所有文库中获得，表明针对转谷氨酰胺酶的体液反应发生在局部水平，而针对麦醇溶蛋白的反应则在外周和中枢均有发生。来自所有三名患者的抗体识别相同的转谷氨酰胺酶表位，且偏向于使用V(H)5抗体可变区家族。本文讨论了这些抗转谷氨酰胺酶抗体在CD发病及相关自身免疫性疾病中的可能作用。
