At least 3 different autoimmune disorders may cause neuromyelitis optica spectrum disorder (NMOSD), according to a study recently published in Frontiers in Immunology.

“We found that major histocompatibility complex I class I-related biological processes and interferon-gamma-mediated signaling pathway may be involved in the pathogenesis of NMOSD coexisting with autoimmune thyroid disease, systemic lupus erythematosus, and Sjogren’s syndrome,” the authors wrote.

This observational study evaluated data from genome-wide association studies regarding NMOSD and 3 other autoimmune diseases—systemic lupus erythematosus, Sjogren’s syndrome, and autoimmune thyroid disease. After analyzing causal single-nucleotide polymorphisms and cis-expression quantitative trait loci, a pathway enrichment analysis aimed to investigate a causal relationship between NMOSD and these entities.


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Using a 2 sample Mendelian randomization method, all 3 autoimmune disorders showcased a causal association with NMOSD. Interestingly, the reverse relationship did not occur. Furthermore, the study observed that major histocompatibility complex I and interferon-gamma signaling pathways played a key role in the etiology of NMOSD, systemic lupus erythematosus, Sjogren’s syndrome, and autoimmune thyroid disease, as determined by a Gene Ontology enrichment analysis.

Lastly, the authors performed an analysis of the Comparative Toxicogenomics Database to identify potential drugs based on their ability to inhibit the biological activity of cis-expression quantitative trait loci.

A total of 30 molecules met the criteria, including various anticancer and antiviral agents, proteasome inhibitors, anticoagulants, immunosuppressive drugs, and natural compounds, as well as 1 agent from each of the following categories: Janus kinase inhibitor, histone deacetylase inhibitor, protein kinase c activator, beta-adrenergic receptor antagonist, and enzyme inhibitor.

These findings could guide further research on assessing therapeutic options effective for treating coexisting conditions. Perhaps the most promising drug could be dimethyl fumarate (DMF), previously used for multiple sclerosis as disease-modifying therapy.

“DMF mainly suppresses the function of interferon gamma and reduces the proportion of circulating Th1, and our current study revealed that the interferon-gamma-mediated pathway was involved in NMOSD coexisting with autoimmune disorders,” the authors explained.

Reference

Wang X, Shi Z, Zhao Z, et al. The causal relationship between neuromyelitis optica spectrum disorder and other autoimmune diseases. Front Immunol. Published online September 29, 2022. doi:10.3389/fimmu.2022.959469