Anti‐Endothelial Antibodies and Neuropsychiatric Systemic Lupus Erythematosus

Abstract

The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) has been attributed to autoantibody-mediated neural dysfunction, vasculopathy, and coagulopathy. Several autoantibodies specificities have been reported in serum and cerebrospinal fluid of NPSLE patients (i.e., antineuronal, antiribosomal P proteins, antiglial fibrillary acidic proteins, antiphospholipid, and anti-endothelial antibodies). We have recently demonstrated an association between serum anti-endothelial antibodies and psychosis or depression in patients with SLE. Subsequently, by screening a cDNA library from human umbilical artery endothelial cells with serum from a SLE patient with psychosis, one positive strongly reactive clone was identified encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family. Anti-Nedd5 antibodies have been found significantly associated with psychiatric manifestations in SLE patients, strengthening the view of a possible implication of autoantibodies in the development of psychiatric disorders.

Late Consequences of Chronic Pediatric Illness

“…Several autoantibodies have been reported in serum and cerebrospinal fluid, including anti-neuronal, anti-ribosomal P proteins, anti-glial fibrillary acidic proteins, anti-phospholipid, and anti-endothelial antibodies [75]. Anti-Nedd5 antibodies have been found to be associated with psychosis in SLE patients [75].…”

“…Several autoantibodies have been reported in serum and cerebrospinal fluid, including anti-neuronal, anti-ribosomal P proteins, anti-glial fibrillary acidic proteins, anti-phospholipid, and anti-endothelial antibodies [75]. Anti-Nedd5 antibodies have been found to be associated with psychosis in SLE patients [75]. Anti-Nmethyl-D-aspartate receptor antibodies have been associated with neuropsychiatric symptoms in SLE, but their presence alone does not explain cognitive dysfunction, depression, or anxiety in patients with SLE [76].…”

Neuroimmunopathology in a murine model of neuropsychiatric lupus

“…Indeed, deposition of antigen-antibody complexes (immune aggregates) in choroidal blood vessels have been associated with neuropsychiatric dysfunction, and vascular deposits within the choroid plexus (CP) are accompanied by histopathologic evidence of inflammation (Schwartz and Roberts, 1983). Therefore, autoantibodies to endothelial cells, as well as the pathogenic action of circulating-immune complexes (CIC) on microvessels, likely contribute to, if not cause, endothelial cell damage and breakdown of the BBB in lupus patients and mice (Valesini et al, 2006;Hoffman et al, 1983;Ma et al, 2006).…”

Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers

“…Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystemic involvement presenting with numerous clinical manifestations [1]. Neuropsychiatric systemic lupus erythematosus (NPSLE) involves neurologic manifestations seen in the central, peripheral, and autonomic nervous systems as well as psychiatric disorders in patients with SLE in which other causes have been excluded [1,2].…”

“…Neuropsychiatric systemic lupus erythematosus (NPSLE) involves neurologic manifestations seen in the central, peripheral, and autonomic nervous systems as well as psychiatric disorders in patients with SLE in which other causes have been excluded [1,2]. In 1999, an international multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology established case definitions for 19 neuropsychiatric syndromes including diagnostic criteria, important exclusions, and methods of ascertainment (Table 1) [2].…”