Hans Christian Andersen Children's Hospital, Odense University Hospital, University of Southern Denmark, Denmark; Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, Denmark.
Hans Christian Andersen Children's Hospital, Odense University Hospital, University of Southern Denmark, Denmark; Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, Denmark.
Clin Immunol. 2014 Aug;153(2):323-31. doi: 10.1016/j.clim.2014.05.009. Epub 2014 Jun 3.
Celiac disease (CD) is characterized by an inappropriate immunological reaction against gluten driven by gluten-specific CD4+ T cells. We screened 25 proteases and tested 10 for their potential to degrade gluten in vitro. Five proteases were further tested for their ability to prevent the proliferative response by a gluten-specific CD4+ T cell clone and seven gluten-reactive T cell lines to protease-digested gluten peptides. A proline-specific endo-peptidase from Aspergillus niger (AnP2) was particularly efficient at diminishing proliferation after stimulation with cleaved antigen, and could completely block the response against both native and deamidated gluten peptides. We found that AnP2 was efficient down to a 1:64 protease:substrate ratio (w:w). When AnP2 was tested in assays using seven gluten-reactive T cell lines from individual CD patients (three adults and four children), the response to gluten was diminished in all cases. Our study indicates a therapeutic benefit of AnP2 to CD patients.
乳糜泻（CD）的特征是由针对麸质的 CD4+T 细胞引起的针对麸质的不适当免疫反应。我们筛选了 25 种蛋白酶，并测试了其中 10 种在体外降解麸质的潜力。进一步测试了 5 种蛋白酶，以检测它们对麸质特异性 CD4+T 细胞克隆和 7 种对蛋白酶消化的麸质肽有反应性的 T 细胞系的增殖反应的抑制作用。来自黑曲霉（Aspergillus niger）的一种脯氨酸特异性内切肽酶（AnP2）在对切割抗原的刺激后抑制增殖的效果特别好，并且可以完全阻断对天然和脱酰胺麸质肽的反应。我们发现，AnP2 在 1:64 的蛋白酶：底物比例（w:w）下仍有效。当在来自单个 CD 患者的 7 个对麸质有反应性的 T 细胞系的测定中测试 AnP2 时，所有情况下对麸质的反应均减弱。我们的研究表明 AnP2 对 CD 患者有治疗益处。
