Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein-1 Shows Promise as Predictor for Severity of Acute AQP4-IgG NMOSD

Findings from a North China-based study showed that plasma aminoacyl-tRNA synthetase complex interacting with multifunctional protein-1 (AIMP1) levels were higher in AQP4-IgG positive neuromyelitis optica spectrum disorder (NMOSD) in the acute phase before intravenous methylprednisolone (IVMP) therapy than in healthy controls (HC), suggesting a role in the pathogenesis of the disease.

Data showed that the plasma levels of AIMP1 were significantly higher in patients with AQP4-IgG+ NMOSD (n = 94) than in HCs (n = 33; P < 0.001). Notably, the plasma AIMP1 levels in patients with AQP4-IgG+NMOSD in the acute phase before IVMP therapy were significantly higher in comparison with those after the IVMP therapy (P <.001) as well as those in the clinical remission phase (P = .021) or HCs (P <.001). Additionally, the plasma AIMP1 levels of patients in the remission phase were lower than patients in the acute-phase NMOSD prior to IVMP (P = 0.021) and higher than HCs (P < 0.001).

“Plasma AIMP1 levels appear to be a possible promising predictor of the severity of NMOSD disease,” senior author Bin Lin, MD, professor of neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China, and colleagues wrote.¹ “It also seems to serve as a meaningful dynamic indicator of disease activity and treatment effectiveness in patients with acute AQP4-IgG+ NMOSD.”

A total of 92 patients with AQP4-IgG+ NMOSD were recruited between March 2021 and May 2022 from The Second Hospital of Hebei Medical University in North China based on diagnostic criteria.2 Among the enrolled patients, 48 were in the acute phase before high-dose IVMP therapy, 21 were in the acute phase after IVMP therapy, and 25 were in the clinical remission-phase, along with 33 HCs. The plasma AIMP1 levels were measured using ELISA kits while disability function was evaluated using the Expanded Disability Status Scale (EDSS) scoreIn addition, clinical characteristics were evaluated, and laboratory blood tests were performed. The mean age of patients with NMOSD was 46.53 (±15.83) years, predominantly women (92.6%), and the average age at the first onset of NMOSD was 42.12 (±16.61) years.

Results further demonstrated that plasma AIMP1 levels in the relapse and first episode groups of acute NMOSD were significantly higher compared with HCs (P <.001, P <.001, respectively). The plasma AIMP1 levels in patients with acute AQP4-IgG+NMOSD with EDSS scores of at least 4 were significantly higher than patients with EDSS less than 4 and HCs groups (P = 0.001, P <.001, respectively). In addition, these levels were higher for patients with acute NMOSD with EDSS less than 4 as compared with HCs (P = 0.002).

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“We were unable to compare plasma AIMP1 levels before and after relapse. However, our results showed that plasma AIMP1 levels in patients with acute NMOSD after relapse were significantly elevated compared to that in HCs, and were positively correlated with increased EDSS scores. The results implied that relapse could worsen disease severity, and AIMP1 was associated with the severity of new neurological dysfunction after relapse,” Bin et al noted.¹

In a correlation analysis, plasma AIMP1 levels were positively correlated with EDSS score (r = 0.485, P < 0.001) and increased EDSS score (r = 0.576, P < 0.001), but not the baseline EDSS score (r = 0.191, P = 0.192) in patients with acute AQP4-IgG+NMOSD. In both the univariate and multivariate analyses, plasma AIMP1 levels of at least or 49.55 pg/mL (OR 0.03, 95%CI 0.001–0.645, P = 0.026) displayed to be an independent predictor for the severity of NMOSD.

Bin et al noted, “It is well known that immuno-inflammatory activation plays a central role in the pathophysiological processes of NMOSD. AIMP1 has been recognized for its prominent immunological functions.”¹

Limitations in the study included sample size as some factors, potentially meaningful, could not be analyzed for differences. Additionally, the findings of the study may only represent a small part of the general Chinese population of patients with AQP4-IgG+NMOSD. Thus, authors noted that the sample size should be expanded further and despite the small sample, the study showed the potential of AIMP1 in predicting the severity of the disease.

REFERENCES
1. Yuan C, Liu X, Cai S, et al. Secreted aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) is a promising predictor for the severity of acute AQP4-IgG positive neuromyelitis optica spectrum disorder. Published January 4, 2023. Mult Scler Relat Disord. 2023;70:104504. doi:10.1016/j.msard.2023.104504
2. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/WNL.0000000000001729