Alternation of anti-NMDA receptor subunit GluN2 antibody in a patient with SLE who promptly developed anxiety after belimumab

We report a 29-year-old female with systemic lupus erythematosus (SLE) who promptly developed anxiety after belimumab. She was diagnosed as SLE due to fever, general fatigue, polyarthritis, hypocomplementemia, and positivity of antinuclear antibody and anti-dsDNA antibody, and hydroxychloroquine (HCQ) monotherapy was initiated. Fourteen months following HCQ introduction, arthritis recurred, prednisolone (PSL) 5 mg/day and methotrexate were added. However, since her arthritis recurred during PSL tapering, we added BEL. Three months later, she developed morbid anxiety evaluated by a psychiatrist with protein elevation, interleukin (IL)-6 15.4 pg/mL, anti-neuronal cell antibody (anti-N) 0.66 U/mL (normal <0.27) and autoantibody against anti-N-methyl-D-aspartate receptor subunit GluN2A/B (anti-GluN2) 0.12 U/mL (normal <0.10) in cerebrospinal fluid (CSF). Therefore, we discontinued BEL in consideration of both adverse event in association with BEL as well as neuropsychiatric SLE development. Two months later, her anxiety almost completely disappeared with decreased IL-6 7.0 pg/mL, anti-N 0.36 U/mL and anti-GluN2 0.02 U/mL. As far, no psychiatric manifestation has been developed. Our case indicate that BEL may involve paradoxical elevation of autoantibodies against neurons in the central nervous system, causing neuronal inflammation. Exhaustive investigation of CSF biomarkers could be an important strategy to investigate the pathophysiology of psychiatric manifestations due to BEL.