Abstract Details

Title MALT1 Scaffold and Proteolytic Activity Regulate Tfh Cell Differentiation in the Progression of Neuromyelitis Optica

Topic Autoimmune Neurology

Presentation(s) S38 - NMOSD, MOGAD, Demyelinating, and Other (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Objective This study aims to elucidate the interplay between MALT1 and the pathogenesis of neuromyelitis optica (NMO).

Background The mucosa-associated lymphoid tissue lymphoma translation protein 1 (MALT1) lays a multifaceted role in immune and inflammatory responses. Despite its established functions, the specific contribution of MALT1 to NMO pathogenesis remains enigmatic. MALT1 serves as a scaffold protein within the NF-κB signaling pathway and has recently been identified to possess proteolytic capabilities, modulating the fate of Tfh cells by cleaving proteins such as Roquin-1. However, the impact of MALT1 on distinct T cell subsets appears to be context-dependent.

Design/Methods We conducted a comprehensive analysis of peripheral blood mononuclear cells (PBMCs) from 30 NMO patients with verified diagnoses and complete clinical profiles (15 during acute episodes and 15 in remission), along with 15 healthy controls. Flow cytometry was employed to quantify the frequency of CD3⁺CD4⁺CXCR5⁺PD-1⁺Tfh cells in the peripheral circulation. RT-qPCR was utilized to assess the expression of key genes in CD4⁺T cells, including MALT1, Roquin-1, ICOS, etc. Additionally, MALT1’s proteolytic activity was evaluated using western blot analysis.

Results

Our findings revealed that, compared to healthy controls, the mRNA levels of MALT1 were significantly elevated in CD4⁺T cells from acute NMO patients, while Roquin-1 expression was markedly reduced (P<0.05). Intriguingly, MALT1 expression level correlated positively with Expanded Disability Status Scale scores, annual relapse rates , magnetic resonance imaging lesion counts, and the proportion of circulating Tfh cells (P<0.05). Furthermore, Roquin-1 in the CD4⁺T cells of patients during acute phase was predominantly observed as cleaved fragments, suggesting an augmented MALT1 proteolytic activity in NMO.

Conclusions

Collectively, our data suggest that both the scaffold and proteolytic functions of MALT1 influence the clinical severity of NMO. MALT1 may contribute to NMO pathogenesis by modulating Tfh cell differentiation through the MALT1-Roquin-1 axis, thereby impacting disease progression.

Authors/Disclosures
Ruoyu Li PRESENTER	Miss Li has nothing to disclose.
Hongbo Liu (the First Affiliated Hospital of Zhengzhou University, Zhengzhou University)	The institution of Hongbo Liu has received research support from China.

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