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Open AccessArticle

Differential Expression of Tissue Transglutaminase Splice Variants in Peripheral Blood Mononuclear Cells of Primary Progressive Multiple Sclerosis Patients

1
Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands
2
Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands
3
Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Med. Sci. 2018, 6(4), 108; https://doi.org/10.3390/medsci6040108
Received: 30 October 2018 / Revised: 20 November 2018 / Accepted: 22 November 2018 / Published: 27 November 2018
(This article belongs to the Special Issue Transglutaminases in Health and Disease)
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. View Full-Text
Keywords: Tissue transglutaminase; alternative splicing; multiple sclerosis; peripheral blood mononuclear cells (PBMC) Tissue transglutaminase; alternative splicing; multiple sclerosis; peripheral blood mononuclear cells (PBMC)
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Sestito, C.; Brevé, J.J.P.; Killestein, J.; Teunissen, C.E.; Wilhelmus, M.M.M.; Drukarch, B.; Van Dam, A.-M. Differential Expression of Tissue Transglutaminase Splice Variants in Peripheral Blood Mononuclear Cells of Primary Progressive Multiple Sclerosis Patients. Med. Sci. 2018, 6, 108.

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