The lncRNA 74.1/miR-324-3p/NRG1 axis as a differential diagnostic and prognostic biomarker in neuromyelitis optica and multiple sclerosis.

BACKGROUND

Multiple sclerosis (MS) and Neuromyelitis Optica (NMO) are complex, multifactorial diseases that often present with similar clinical symptoms, leading to frequent misdiagnosis, especially in cases where NMO is aquaporin-4 seronegative. Identifying the mechanisms underlying MS may help uncover disease biomarkers and facilitate timely diagnosis, and MS treatment. There is an urgent need for differential diagnostic and prognostic tools for these devastating diseases to ensure appropriate therapy and improve patient outcomes.

METHODS

This study enrolled 252 participants, divided into four groups. Group I (Relapsing-Remitting MS: RRMS group), Group II (Secondary Progressive MS: SPMS group), Group III (NMO group), and Group IV (Healthy controls), with matched age and sex. Blood samples were collected from all participants for determination of serum NRG1. Total RNA was also extracted from the whole blood then utilized for cDNA synthesis, qPCR was performed and the expression levels of lncRNA 74.1 and miR-324-3p were calculated.

RESULTS

NRG1 levels were significantly lower in all patient groups (RRMS, SPMS, NMO) compared to healthy controls (p-values <0.05), with the most pronounced reduction observed in NMO. ROC curve analysis indicated that NRG1 could distinguish NMO from MS with an accuracy (AUC) of 0.70. miR-324-3p was notably upregulated in RRMS and NMO compared to controls and showed strong potential in differentiating NMO from other conditions. A significant difference in miR-324-3p was observed between RRMS and SPMS (p = 0.0012). In contrast, lncRNA 74.1 did not exhibit significant diagnostic or prognostic value across the groups. Correlation analyses revealed no significant relationships between NRG1 and miR-324-3p or lncRNA 74.1 in any patient group, though a significant positive correlation was found between lncRNA 74.1 and miR-324-3p in NMO and healthy controls.

CONCLUSION

In this study, we reaffirm the previously observed reduction in NRG1 levels in NMO patients but extend these findings by elucidating a novel regulatory axis involving lncRNA 74.1 and miR-324-3p. Our results highlight NRG1 as a valuable biomarker with strong potential to improve diagnostic differentiation between MS and NMO, particularly in cases where conventional diagnostics are inconclusive. Moreover, we identify miR-324-3p as a promising marker for distinguishing RRMS from other phenotypes, with possible prognostic value in predicting transition to SPMS. Together, these findings not only support the diagnostic relevance of NRG1 but also introduce new mechanistic insights that may enhance both diagnostic precision and future therapeutic strategies.