Pathogenesis of neuropsychiatric lupus

Erica Moore, Ayal Ben-Zvi, Chaim Putterman

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Many avenues of research have been pursued to clarify the pathogenic mechanisms underlying the development of diffuse neuropsychiatric systematic lupus erythematosus (NPSLE). Given their overall importance in systemic lupus erythematosus, the identification of specific autoreactive antibodies associated with NPSLE has been aggressively sought. Besides lupus autoantibodies specific for systemically expressed or brain antigenic determinants, there is also increasing interest in serologic reactivity with neuronal antigens reflecting particular clinical syndromes and presentations. The leading candidate autoantibodies appear to be anti-NMDAR and anti-P antibodies, which have repeatedly (albeit somewhat variably) been associated with NPSLE, both in human patients and mouse models. However, this inconsistency may represent an underappreciated facet of NPSLE pathogenesis, namely that the source of immune penetrance into the central nervous system (CNS) is unclear. Furthermore, the potential for CNS-derived aberrant immunity (i.e., local production of neurotoxic antibodies and other pathogenic mediators) tends to be discounted. When factoring in cytokine and chemokine contributors to its overall pathogenesis, it is clear that NPSLE is a remarkably complex manifestation of SLE. It is more than likely that several mechanisms may be concurrently engaged in the development of NPSLE and that various combinations of disease-related pathways can potentially contribute to the diverse neuropsychiatric presentations found in lupus patients.

Original languageEnglish
Title of host publicationDubois' Lupus Erythematosus and Related Syndromes
PublisherElsevier
Pages338-348
Number of pages11
ISBN (Electronic)9780323932325
DOIs
StatePublished - 1 Jan 2024

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Inc. All rights reserved.

Keywords

  • Neuropsychiatric lupus
  • anti-NMDAR
  • antiribosomal P
  • blood-brain barriers
  • choroid plexus

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