2024 American Academy of Neurology Abstract Website

Objective:

To target the molecular and cellular mechanism associated with relapsing anti-NMDAR encephalitis.

Background:

Anti-NMDAR encephalitis is a rapidly progressive encephalopathy syndrome. Previous studies reported approximately 16% of relapsing anti-NMDAR encephalitis, and the mechanism of relapse is uncertain.

Design/Methods:

We enrolled patients diagnosed with anti-NMDAR encephalitis in West China Hospital, Sichuan University, and collected their clinical data and samples from bone marrow and peripheral blood of patients. The variation of B cell subpopulations in the samples was then evaluated by flow cytometry.

Results:

1. 283 anti-NMDAR encephalitis patients were enrolled, of whom 17.31% had at least one relapse. 2. A paired test for anti-NMDAR antibody titers in bone marrow, peripheral blood, and cerebrospinal fluid supernatant was completed in 10 patients, of whom 90% had positive bone marrow titers. 3. Flow cytometry was used to detect variation of 12 patients with relapsed acute and stable anti-NMDAR encephalitis, and the results showed that the proportion of unconverted memory B-cells was higher in the bone marrow of patients with relapsed acute disease (Me=11.95%, IQR=5.08%-22.48%) than in patients with stable disease (Me= 4.18%, IQR= 2.88%- 8.02%), the proportion of transformed memory B cells (Me= 13.45%, IQR= 8.57%- 21.28%) was higher than that of stable patients (Me= 7.72%, IQR= 5.53%- 22.85%), and the proportion of plasma cells (Me= 6.64%, IQR= 0.98%- 11.34%) was lower than that of stable patients (Me= 10.92%. IQR= 2.74%- 19.93%), and the percentage of long-lived plasma cells (Me= 5.00%, IQR= 0.66%- 7.80%) was lower than that of stable patients (Me= 7.40%, IQR= 1.61%- 14.39%).

Conclusions:

1.There were probably antigen-specific plasma cells in the bone marrow of anti-NMDAR encephalitis secreting autoantibodies involved in the pathogenesis.

2. Long-lived plasma cells were depleted during relapse in patients with anti-NMDAR encephalitis, and memory B cells may be homed to the bone marrow after being activated to undergo clonal expansion.