Sander J Deijns1, Jasper C A Broen2, Nyika D Kruyt3, Chris D Schubart4, Laura Andreoli5, Angela Tincani6, Maarten Limper7. 1. University Medical Centre Utrecht and Utrecht University, Utrecht 3584 CX, the Netherlands. 2. Regional Rheumatology Centre, Máxima Medical Centre, 5631 BM Eindhoven and 5504 DB, Veldhoven, the Netherlands. 3. Department of Neurology, Leiden University Medical Centre, Leiden 2333 ZA, the Netherlands. Electronic address: n.d.kruyt@lumc.nl. 4. Department of Psychiatry, Tergooi Ziekenhuis, 1261 AN Blaricum, Hilversum 1213 XZ, the Netherlands. Electronic address: CSchubart@tergooi.nl. 5. Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, BS 25123, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, BS 25123, Italy. Electronic address: Laura.Andreoli@unibs.it. 6. Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, BS 25123, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, BS 25123, Italy; I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address: Angela.Tincani@unibs.it. 7. Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht 3584 CX, the Netherlands. Electronic address: M.Limper-2@umcutrecht.nl.
Abstract
INTRODUCTION: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: A systematic search on PubMed was conducted. English studies with full text availability that investigated the correlation between blood-brain barrier (BBB) dysfunction, intrathecal synthesis of antibodies, antibodies, cytokines, chemokines, metalloproteinases, complement and psychiatric NPSLE manifestations in adults were included. RESULTS: Both transient BBB-dysfunction with consequent access of antibodies to the cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies could occur in psychiatric NPSLE. Anti-phospholipid antibodies, anti-NMDA antibodies and anti-ribosomal protein p antibodies seem to mediate concentration dependent neuronal dysfunction. Interferon-α may induce microglial engulfment of neurons, direct neuronal damage and production of cytokines and chemokines in psychiatric NPSLE. Several cytokines, chemokines and matrix metalloproteinase-9 may contribute to the pathophysiology of psychiatric NPSLE by attracting and activating Th1-cells and B-cells. DISCUSSION: This potential pathophysiology may help understand NPSLE and may have implications for the diagnostic management and therapy of psychiatric NPSLE. However, the presented pathophysiological model is based on correlations between potential immunologic etiologies and psychiatric NPSLE that remain questionable. More research on this topic is necessary to further elucidate the pathophysiology of NPSLE.
INTRODUCTION: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: A systematic search on PubMed was conducted. English studies with full text availability that investigated the correlation between blood-brain barrier (BBB) dysfunction, intrathecal synthesis of antibodies, antibodies, cytokines, chemokines, metalloproteinases, complement and psychiatric NPSLE manifestations in adults were included. RESULTS: Both transient BBB-dysfunction with consequent access of antibodies to the cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies could occur in psychiatric NPSLE. Anti-phospholipid antibodies, anti-NMDA antibodies and anti-ribosomal protein p antibodies seem to mediate concentration dependent neuronal dysfunction. Interferon-α may induce microglial engulfment of neurons, direct neuronal damage and production of cytokines and chemokines in psychiatric NPSLE. Several cytokines, chemokines and matrix metalloproteinase-9 may contribute to the pathophysiology of psychiatric NPSLE by attracting and activating Th1-cells and B-cells. DISCUSSION: This potential pathophysiology may help understand NPSLE and may have implications for the diagnostic management and therapy of psychiatric NPSLE. However, the presented pathophysiological model is based on correlations between potential immunologic etiologies and psychiatric NPSLE that remain questionable. More research on this topic is necessary to further elucidate the pathophysiology of NPSLE.