Department of Gastroenterology, Dayanand Medical College, Ludhiana, India.
School of Agriculture Biotechnology, Punjab Agricultural University, Ludhiana, India.
Front Immunol. 2019 Feb 4;10:84. doi: 10.3389/fimmu.2019.00084. eCollection 2019.
Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed.
乳糜泻(CD)是一种多因素的自身免疫性肠病,由携带 HLA DQ2/8 基因的遗传易感个体的谷物蛋白激活。不同小麦基因型中有记录的谷物醇溶蛋白的杂合基因组合表明其具有不同的免疫原性。在目前的研究中,通过分析鉴定了四种小麦品种(C591、C273、9D 和 K78),通过测量 T 细胞增殖率和炎症细胞因子(干扰素-γ和肿瘤坏死因子-α)水平来分析其免疫原性。从四名完全缓解的 CD 患者和两名对照者中分离出外周血单核细胞和活检衍生的 T 细胞系,在组织转谷氨酰胺酶激活的胃蛋白酶-胰蛋白酶(PT)消化物存在下刺激和培养测试品种的总麦醇溶蛋白提取物。将免疫原性与广泛种植的小麦品种之一 PBW 621 进行比较。植物血球凝集素-p 被用作阳性对照,未刺激的细胞作为阴性对照。细胞增殖率(0.318、0.482;0.369、0.337)、IFN-γ浓度(107.4、99.2;117.9、99.7 pg/ml)和 TNF-α浓度(453.8、514.2;463.8、514.2 pg/ml)在补充 C273 小麦抗原的培养物中最低,与其他测试品种和未刺激的细胞相比。不同小麦基因型对刺激乳糜泻黏膜 T 细胞和 PBMC 的毒性水平有显著差异;其中 C273 在分析的测试品种中表现出最低的免疫原性反应。