Sestito Claudia, Brevé John J P, Killestein Joep, Teunissen Charlotte E, Wilhelmus Micha M M, Drukarch Benjamin, van Dam Anne-Marie
Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.
Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.
Med Sci (Basel). 2018 Nov 27;6(4):108. doi: 10.3390/medsci6040108.
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS) characterized by inflammation and immune cell infiltration in the brain parenchyma. Tissue transglutaminase (TG2), a calcium-dependent cross-linking enzyme, has been shown to be present in infiltrating MHC-II positive cells in lesions of patients suffering from MS. Moreover, TG2 mRNA levels in peripheral blood mononuclear cells (PBMC)-derived from primary progressive (PP)-MS patients correlated with clinical parameters, thus highlighting the importance of TG2 in MS pathology. In the present study, we further characterized TG2 expression by measuring the mRNA levels of full-length TG2 and four TG2 alternative splice variants in PBMCs derived from PP-MS patients and healthy control (HC) subjects. In PP-MS-derived PBMCs, TG2 variant V4b was significantly higher expressed, and both V4a and V4b variants were relatively more expressed in relation to full-length TG2. These observations open new avenues to unravel the importance of TG2 alternative splicing in the pathophysiology of PP-MS.
多发性硬化症（MS）是一种中枢神经系统（CNS）的炎症性和神经退行性疾病，其特征是脑实质出现炎症和免疫细胞浸润。组织转谷氨酰胺酶（TG2）是一种钙依赖性交联酶，已证实在患有MS的患者病变中浸润的MHC-II阳性细胞中存在。此外，源自原发性进行性（PP）-MS患者的外周血单核细胞（PBMC）中的TG2 mRNA水平与临床参数相关，从而突出了TG2在MS病理学中的重要性。在本研究中，我们通过测量源自PP-MS患者和健康对照（HC）受试者的PBMC中全长TG2和四种TG2可变剪接变体的mRNA水平，进一步表征了TG2的表达。在源自PP-MS的PBMC中，TG2变体V4b表达明显更高，并且相对于全长TG2，V4a和V4b变体表达相对更多。这些观察结果为揭示TG2可变剪接在PP-MS病理生理学中的重要性开辟了新途径。
