Use of Transglutaminase 2 mRNA expression in peripheral blood mononuclear cells in patients with Radiologically Isolated Syndrome as a neuroinflammation biomarker: A preliminary study

Rosa Giacca; Miriana Conte; Alessandro d'Ambrosio; Alvino Bisecco; Renato Docimo; Mario Risi; Manuela Altieri; Riccardo Borgo; Rosario Domenico Melisi; Vittorio Gentile; Antonio Gallo; Rosa Giacca; Miriana Conte; Alessandro d'Ambrosio; Alvino Bisecco; Renato Docimo; Mario Risi; Manuela Altieri; Riccardo Borgo; Rosario Domenico Melisi; Vittorio Gentile; Antonio Gallo

doi:10.3934/Neuroscience.2025015

AIMS Neuroscience

2025, Volume 12, Issue 2: 284-290. doi: 10.3934/Neuroscience.2025015

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Use of Transglutaminase 2 mRNA expression in peripheral blood mononuclear cells in patients with Radiologically Isolated Syndrome as a neuroinflammation biomarker: A preliminary study

1.
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
2.
First Division of Neurology and Neurophysiopathology, AOU “Luigi Vanvitelli”, Naples, Italy
3.
Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
4.
Interuniversity Center of Neuroscience Researches (CIRN), University of Campania “Luigi Vanvitelli”, Naples, Italy
These two authors contributed equally.

Received: 02 May 2025 Revised: 10 June 2025 Accepted: 20 June 2025 Published: 24 June 2025

The calcium-dependent enzyme Transglutaminase 2 (TG2) (E.C. 2.3.2.13), which can promote post-translational modifications of proteins, is involved in several physiological processes, including development, neuronal cell death, and differentiation, as well as synaptic plasticity and transmission in the central nervous system (CNS). Several studies highlight the potential role of the TG2/NF-κB activation pathway in neurodegenerative diseases, including Multiple Sclerosis (MS), and the neuroinflammation that is associated with these conditions. The cross-linking activity of TG2, facilitating the formation of isopeptide bonds between glutamine and lysine residues, appears to be involved in forming protein aggregate deposits in these pathological conditions. Specifically, in the chronic neuroinflammation of MS, TG2 seems to play a central role in the fibrotic process of the lesion. Several potential biomarkers have been investigated for the prognosis and monitoring of MS, but no researchers have explored the presence of potential inflammatory signals in peripheral blood mononuclear cells (PBMCs) during the presymptomatic stage of MS, known as Radiologically Isolated Syndrome (RIS), on account of the lack of information regarding its pathological aspects. Since researchers have demonstrated a correlation between TG2 mRNA levels in PBMCs and the clinical and radiological progression of MS, we aimed to evaluate the expression levels of TG2 in RIS patients, comparing them with those in relapsing-remitting MS (RRMS) patients and healthy controls (HCs) using real-time PCR analysis. Preliminary data showed that RIS patients exhibit lower TG2 mRNA expression levels compared to RRMS patients, while no difference in TG2 mRNA expression being observed between RIS patients and HCs. This suggests that RIS patients exhibit a lower neuroinflammation grade than RRMS patients and that TG2 may represent a potential biochemical marker for assessing neuroinflammation associated with this disease. Future investigations may include longitudinal assessments of the potential role of TG2 mRNA blood levels in predicting or monitoring the progression from RIS to MS.
- transglutaminase 2,
- multiple sclerosis,
- radiologically isolated syndrome,
- neuroinflammation,
- biomarker
Citation: Rosa Giacca, Miriana Conte, Alessandro d'Ambrosio, Alvino Bisecco, Renato Docimo, Mario Risi, Manuela Altieri, Riccardo Borgo, Rosario Domenico Melisi, Vittorio Gentile, Antonio Gallo. Use of Transglutaminase 2 mRNA expression in peripheral blood mononuclear cells in patients with Radiologically Isolated Syndrome as a neuroinflammation biomarker: A preliminary study[J]. AIMS Neuroscience, 2025, 12(2): 284-290. doi: 10.3934/Neuroscience.2025015

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Abstract

The calcium-dependent enzyme Transglutaminase 2 (TG2) (E.C. 2.3.2.13), which can promote post-translational modifications of proteins, is involved in several physiological processes, including development, neuronal cell death, and differentiation, as well as synaptic plasticity and transmission in the central nervous system (CNS). Several studies highlight the potential role of the TG2/NF-κB activation pathway in neurodegenerative diseases, including Multiple Sclerosis (MS), and the neuroinflammation that is associated with these conditions. The cross-linking activity of TG2, facilitating the formation of isopeptide bonds between glutamine and lysine residues, appears to be involved in forming protein aggregate deposits in these pathological conditions. Specifically, in the chronic neuroinflammation of MS, TG2 seems to play a central role in the fibrotic process of the lesion. Several potential biomarkers have been investigated for the prognosis and monitoring of MS, but no researchers have explored the presence of potential inflammatory signals in peripheral blood mononuclear cells (PBMCs) during the presymptomatic stage of MS, known as Radiologically Isolated Syndrome (RIS), on account of the lack of information regarding its pathological aspects. Since researchers have demonstrated a correlation between TG2 mRNA levels in PBMCs and the clinical and radiological progression of MS, we aimed to evaluate the expression levels of TG2 in RIS patients, comparing them with those in relapsing-remitting MS (RRMS) patients and healthy controls (HCs) using real-time PCR analysis. Preliminary data showed that RIS patients exhibit lower TG2 mRNA expression levels compared to RRMS patients, while no difference in TG2 mRNA expression being observed between RIS patients and HCs. This suggests that RIS patients exhibit a lower neuroinflammation grade than RRMS patients and that TG2 may represent a potential biochemical marker for assessing neuroinflammation associated with this disease. Future investigations may include longitudinal assessments of the potential role of TG2 mRNA blood levels in predicting or monitoring the progression from RIS to MS.

Acknowledgments

The author(s) received no financial support for the research, authorship, and/or publication of this article. We thank Prof. Jerome Tessuto for editorial assistance.

Compliance with ethical standards

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent to participate

Written informed consent was obtained from patients for the usage of clinical data in anonymized fashion.

Conflict of interest

The authors declare no conflict of interest.

Authors' contributions

R.G. and M.C.: Methodology and investigation; A.d'A., A.B., R.D., M.R., M.A., R.B., and R.D.M.: Investigation; V.G.: Writing; A.G.: Investigation and review. All authors have read and agreed to the published version of the manuscript.

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