Abstract Details

Title Antibody-Secreting Cells as a Source of NR1-IgGs in N-Methyl-D-Aspartate Receptor-Antibody Encephalitis

Topic Autoimmune Neurology

Presentation(s) S7 - Autoimmune Encephalitis (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is
known, but the immunobiological mechanisms underlying their production remain unclear.

Objective For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum
NR1-IgGs levels.

Design/Methods Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro.

Results For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pregerminal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs.

Conclusions These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.

Authors/Disclosures
Yue Liu (West China Hospital, Sichuan University, Dept of Neurology) PRESENTER	Ms. Liu has nothing to disclose.
Aiqing Li, PhD	Mrs. Li has nothing to disclose.
Linjun Cai, PhD (linjun cai, physician, sichuan university)	Linjun Cai has nothing to disclose.
Zhen Hong (West China Hospital, Sichuan University)	No disclosure on file

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