Decoding Neuropsychiatric Lupus: A Systematic Review of Anti-N-Methyl-D-Aspartate and Anti-ribosomal P Antibodies

Neuropsychiatric systemic lupus erythematosus (NPSLE) includes a wide range of neurological and psychiatric symptoms and is often difficult to diagnose. Autoantibody-mediated neuronal injury has been proposed as a central pathogenic mechanism in NPSLE, particularly involving anti-N-methyl-D-aspartate (NMDA) (anti-NR2/anti-N-methyl-D-aspartate receptor (NMDAR)) antibodies and anti-ribosomal P antibodies. This systematic review evaluated whether these antibodies predict neuropsychiatric or cognitive manifestations in patients with established SLE and assessed their clinical utility for risk stratification. A systematic search of Embase, Web of Science, and Ovid (MEDLINE) identified English-language studies published between January 2015 and December 2025 examining associations between anti-NR2/anti-NMDAR and/or anti-ribosomal P antibodies and neuropsychiatric or cognitive outcomes in SLE. Eighteen studies met the inclusion criteria following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided screening and quality appraisal. Across cohorts, anti-NR2/anti-NMDAR antibodies were most consistently associated with neuropsychiatric phenotypes but showed no reproducible association with objective cognitive impairment or longitudinal cognitive decline. Anti-ribosomal P antibodies showed stronger associations with psychiatric symptom burden. Similarly, anti-ribosomal P positivity was not reliably linked to isolated global cognitive dysfunction. Overall, current evidence suggests that these antibody profiles assist in phenotypic stratification of NPSLE but cannot serve as a standalone predictive biomarker for cognitive impairment. This underscores the need for a multimodal clinical evaluation.