Antinuclear Antibodies Associated With Higher Disability and Disease Severity in NMOSD

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Antinuclear antibodies seem to be more associated with severe disease activity and poor prognosis among patients with NMOSD, which further implies that they may be potentially used as a prognostic marker for the disease.

In a recent published study in the Journal of Neuroimmunology, findings demonstrated that patients with neuromyelitis optica spectrum disorder (NMOSD) who tested positive for antinuclear antibodies (ANAs) had higher disability during the acute phase of the disease and suffered more from severe clinical attacks compared with those with the same condition who tested negative. These results suggest that testing for ANAs among patients with the disease can predict the severity of the relapses and potentially play an important role in the progression and disability of NMOSD.¹

Patients with NMOSD who were positive for ANAs (ANA+; n = 403) had higher Expanded Disability Status Scale (EDSS) scores during the acute stage (4.0 vs. 3.75, P = .013, false discovery rate (FDR) corrected P = .029) and at the final follow-up (P = .032, FDR corrected P = .064). Patients with NMOSD and ANA+ had a higher frequency of severe acute myelitis attack, severe acute myelitis, and optic neuritis attack, motor and visual disability, compared with those who were ANA negative (42.1% vs. 27.8%, P = .001, FDR corrected P = .004, 19.3% vs. 10.3%, P = .004, FDR corrected P = .018, and 11.1% vs. 4.8%, P = .008, FDR corrected P = .022, respectively).

Senior author Hong Yu Zhou, MD, department of neurology, West China Hospital, Sichuan University, Chengdu in China and colleagues investigated ANAs in Chinese patients with NMOSD and their relationship with disease outcomes. Researchers retrospectively collected data from 525 patients diagnosed with NMOSD according to the revised 2015 Wingerchuk criteria for NMOSD,² at West China Hospital between September 1, 2009, and October 1, 2021. The patients were classified into 2 groups of either having NMOSD with ANA+ or ANA-. Both of the groups were compared with each other on their clinical characteristics, relapse rate, severe attacks, laboratory tests, EDSS, and prognosis. The participants were followed-up every 6 months via telephone or in-person interview, finishing in December 2022.

At the conclusion of the analysis, results showed that the NMOSD ANA− group (n = 122) had a lower proportion of motor and visual disability (4.8% vs. 11.1%; P = 0.008, FDR corrected P = .022) than the ANA+ group. Treatment regimens were statistically significant and different between the 2 groups (P = .008). More patients in the ANA− group did not receive immunotherapies compared with the ANA+ group (15.5% vs. 8.3%). Notably, the number of patients who received rituximab in the ANA+ group was higher than that in the ANA− group (14.2% vs. 8.9%).

Investigators also compared 383 ANA+ and ANA− patients with NMOSD who were treated with mycophenolate mofetil or azathioprine. In this analysis, the EDSS scores at the acute stage and final follow-up in the ANA+ patients were higher compared with those without ANA (P <.05). In addition, the ANA− group had a lower proportion of motor disability, motor and visual disability (P <.05) than ANA+ group. The incidence of the EDSS scores greater than or 4 were higher in the ANA positive group than in the negative one (P <.05).

In the study, patients who were seropositive for ANA were more likely to have antiSSA, antiSSB and antiRo-52 antibodies, with positive rates of 46.9% vs 7.4% (P <.001, FDR corrected P <.001), P <.001, FDR corrected P <.001) and 11.0% vs 2.6% (P <.001, FDR corrected p < 0.001), respectively. Furthermore, the AQP4-IgG positive rate was significantly higher in the ANA+ group (n = 191) than in the ANA− group (n = 160)(94.1% vs. 79.3%, P <.001, FDR corrected P <.001).

Researchers also divided the patients with NMOSD into aquaporin-4 (AQP4)-positive (n = 454) and negative (n = 71) groups, and compared the clinical features and outcomes between the groups separately. The AQP4+ patients with NMOSD in the ANA− group had a lower proportion of motor disability, motor and visual disability (P < 0.05) than the ANA+ group, and experienced less severe AM attacks (P <.05) or severe AM and ON attacks (P <.05). The EDSS scores in the acute phase were higher in the AQP4+ and ANA+ patients compared to those in the AQP4+ and ANA− patients (P <.05).

The study was limited by a single research center and researchers did not conduct long-term follow-up of ANA status. In addition, the study also did not analyze the relationship between MRI features and serostatus of ANA. Investigators concluded that the results need to be further validated in larger, multicenter studies.

REFERENCES
1. Wang R, Sun DR, Du Q, et al. Serum antinuclear antibodies associate with severe disease activity in neuromyelitis optica spectrum disorder. J Neuroimmunol. 2023;382:578151. doi:10.1016/j.jneuroim.2023.578151
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