0332: Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) in Cerebrospinal Fluid Relating to Development of Diffuse Psychiatric/Neuropsychological Syndromes in Patients with Systemic Lupus Erythematosus (diffuse NPSLE)

Yoshiyuki Arinuma¹, Yasuhiro Hasegawa², Yu Matsueda², Kenji Oku³ and Kunihiro Yamaoka⁴, ¹Kitasato University, Kanagawa, Japan, ²Kitasato University School of Medicine, Sagamihara, Japan, ³Kitasato University, Chigasaki, Japan, ⁴Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan

Background/Purpose: Microglial activation is critical for behavioral abnormalities in a mouse model of diffuse NPSLE following anti-glutamate receptor subunit GluN2 antibody (anti-GluN2) exposure to neurons. Recently, sTREM2 is known to be the specific activation marker for microglia. The aim of this study is to investigate the potential role of sTREM2 as a factor associating microglial activation with the complication of diffuse NPSLE in patients with SLE.

Methods: Patients with SLE who had collocated NPSLE admitted to our hospital were collected. sTREM2 in serum and cerebrospinal fluid (CSF) were measured by ELISA. Anti-GluN2 was also measured by in house ELISA. Patients and clinical information were collected from medical records. We retrospectively evaluated sTREM2 by NPSLE phenotypes and analyzed the relationship of sTREM2 and anti-GluN2 between diffuse NPSLE and focal neurological manifestations of NPSLE (focal NPSLE).

Results: Twenty-seven patients with diffuse NPSLE and 13 patients with focal NPSLE were recruited in this study. There was no significant difference in serum (p=0.367) and CSF sTREM2 (p=0.936) levels between diffuse and focal NPSLE. Of patients with diffuse NPSLE, CSF sTREM2 in patients with acute confusional state (ACS), the severest form of the diffuse NPSLE was significantly higher (median: 77.6, 0–3328.3 pg/mL) than those without ACS (0, 0–212.1 ng/mL) (p=0.0367) (Figure A). There was no correlation between serum and CSF sTREM2 in patients with diffuse NPSLE (r=0.0887, p=0.660). In addition, sTREM2 index showing the specific presence of sTREM2 in the central nervous system was also significantly elevated in patients with ACS (p=0.023), compared to those without ACS. Remarkably, the CSF sTREM2 levels were significantly correlated with the CSF anti-GluN2 titers (r=0.464, p=0.0394) (Figure B) in patients with diffuse NPSLE, but were not in those with focal NPSLE (r=0.-0584, p=0.876).

Conclusion: The correlation of sTREM2 and anti-GluN2 in CSF from patients with diffuse NPSLE implies that microglia activation is potentially induced after anti-GluN2 exposure in the central nervous system even in humans with diffuse NPSLE.
Figure1 sTREM2 levels and the correlation of anti-GluN2 antibody in patients with diffuse NPSLE
Disclosures: Y. Arinuma, None; Y. Hasegawa, None; Y. Matsueda, None; K. Oku, None; K. Yamaoka, AbbVie GK, Astellas, BMS, Chugai, Mitsubishi-Tanabe, Pfizer, Takeda.