Tissue Transglutaminase Expression Associates With Progression of Multiple Sclerosis

Overview

Journal Neurol Neuroimmunol Neuroinflamm

Specialty Neurology

Date 2021 Apr 28

PMID 33906937

Citations 3

Authors

Claudia Sestito

Cyra E Leurs

Martijn D Steenwijk

John J P Breve

Jos W R Twisk

Micha M M Wilhelmus

Benjamin Drukarch

Charlotte E Teunissen

Anne-Marie Van Dam

Joep Killestein

Affiliations

Soon will be listed here.

Abstract

Objective: The clinical course of multiple sclerosis (MS) is variable and largely unpredictable pointing to an urgent need for markers to monitor disease activity and progression. Recent evidence revealed that tissue transglutaminase (TG2) is altered in patient-derived monocytes. We hypothesize that blood cell-derived TG2 messenger RNA (mRNA) can potentially be used as biomarker in patients with MS.

Methods: In peripheral blood mononuclear cells (PBMCs) from 151 healthy controls and 161 patients with MS, TG2 mRNA was measured and correlated with clinical and MRI parameters of disease activity (annualized relapse rate, gadolinium-enhanced lesions, and T2 lesion volume) and disease progression (Expanded Disability Status Scale [EDSS], normalized brain volume, and hypointense T1 lesion volume).

Results: PBMC-derived TG2 mRNA levels were significantly associated with disease progression, i.e., worsening of the EDSS over 2 years of follow-up, normalized brain volume, and normalized gray and white matter volume in the total MS patient group at baseline. Of these, in patients with relapsing-remitting MS, TG2 expression was significantly associated with worsening of the EDSS scores over 2 years of follow-up. In the patients with primary progressive (PP) MS, TG2 mRNA levels were significantly associated with EDSS, normalized brain volume, and normalized gray and white matter volume at baseline. In addition, TG2 mRNA associated with T1 hypointense lesion volume in the patients with PP MS at baseline.

Conclusion: PBMC-derived TG2 mRNA levels hold promise as biomarker for disease progression in patients with MS.

Classification Of Evidence: This study provides Class II evidence that in patients with MS, PBMC-derived TG2 mRNA levels are associated with disease progression.

Citing Articles

Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.

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Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example.

Lichti C, Wan X Semin Immunol. 2023; 66:101730.

PMID: 36827760 PMC: 10324092. DOI: 10.1016/j.smim.2023.101730.

Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis.

Pearse D, Hefley A, Morales A, Ghosh M Biomedicines. 2022; 10(6).

PMID: 35740263 PMC: 9220003. DOI: 10.3390/biomedicines10061241.

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