Abstract Details

Title Involvement of the Costimulatory Molecules ICOS and OX40 in Neuromyelitis Optica Spectrum Disorder

Topic Autoimmune Neurology

Presentation(s) S6 - Autoimmune Neurology: NMOSD and MOGAD (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Objective This study aims to investigate the expression profiles of ICOS, OX40, and their respective ligands in patients with NMOSD. It also seeks to analyze the relationship between these molecules and disease activity and clinical severity.

Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune disease of the central nervous system mediated by aquaporin-4 antibodies. The key pathological mechanism involves the abnormal activation of T cells and B cells. The costimulatory molecules ICOS/ICOSL and OX40/OX40L play a central role in T cell activation, yet their specific function in NMOSD remains unclear.

Design/Methods A total of 60 NMOSD patients were enrolled, comprising 28 in the acute phase and 32 in the remission phase, alongside 30 healthy controls. Flow cytometry was employed to detect the molecular expression on various peripheral blood cells, including CD4+ T cells, monocytes, and B cells. A specific subset of Tfh cells, identified as CD4+CXCR5+PD-1+, was also analyzed. Disability was scored with EDSS.

Results The results indicated that in patients experiencing an acute NMOSD relapse, the expression of ICOS and OX40 on the surface of CD4+ T cells was significantly upregulated. Concurrently, the expression of their ligands, ICOSL and OX40L, was elevated on monocytes and B cells. Furthermore, the proportion of Tfh cells was significantly increased during the acute phase, and these cells exhibited high expression of OX40. ICOS levels (r = 0.508, P = 0.006) and Tfh proportion (r = 0.465, P = 0.013) correlated positively with EDSS. However, no significant correlation was observed between OX40 expression and the EDSS score.

Conclusions The findings strongly suggest that the ICOS/ICOSL and OX40/OX40L pathways are involved in the acute onset and pathogenesis of NMOSD. The increased proportion of Tfh cells, in particular, may serve as a potential biomarker for monitoring disease activity. These insights offer new avenues for developing targeted therapies for NMOSD.

Authors/Disclosures
Hongbo Liu (the First Affiliated Hospital of Zhengzhou University, Zhengzhou University) PRESENTER	The institution of Hongbo Liu has received research support from China.
Yanmeng Xing	The institution of Dr. Xing has received research support from China.
Xiaojun Yang, MD	Prof. Yang has nothing to disclose.

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