Anti-endothelial-cell
antibodies are associated with psychiatric manifestations in
systemic lupus erythematosus (SLE). Our primary aim in this study was to seek and characterize molecules that behave as endothelial
autoantigens in SLE patients with psychiatric manifestations. By screening a cDNA library from human umbilical artery endothelial cells with serum from an SLE patient with
psychosis, we identified one positive strongly reactive clone encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic
protein of the
septin family. To evaluate anti-Nedd5 serum immunoreactivity, we analyzed by ELISA specific
IgG responses in 17 patients with SLE and psychiatric manifestations (group A), 34 patients with SLE without psychiatric manifestations (group B), 20 patients with
systemic sclerosis, 20 patients with
infectious mononucleosis, and 35 healthy subjects.
IgG specific to Nedd5 C-ter was present in 14 (27%) of the 51 SLE patients. The mean optical density value for
IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients of group A than in those of group B, those with
infectious mononucleosis, or healthy subjects (0.17 +/- 0.14 vs, respectively, 0.11 +/- 0.07, P = 0.04; 0.11 +/- 0.06, P = 0.034; and 0.09 +/- 0.045, P = 0.003, on Student's t-test). Moreover,
IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients with
systemic sclerosis than in patients of group B or healthy subjects (0.18 +/- 0.18 vs, respectively, 0.11 +/- 0.07, P = 0.046; and 0.09 +/- 0.045, P = 0.003). The percentage of patients with anti-Nedd5 C-ter serum
IgG was higher in group A than in group B (8 (47%) of 17, vs 6 (17%) of 34, P = 0.045, on Fisher's exact test). In order to clarify a possible mechanism by which Nedd5 might be autoantigenic, we observed that Nedd5 relocated from cytoplasm to the plasma membrane of EAhy926 endothelial cells after apoptotic stimuli. In conclusion, Nedd5 is a novel
autoantigen of potential clinical importance that could be successfully used for a more thorough investigation of the pathogenesis of psychiatric manifestations in SLE. Although anti-Nedd5
autoantibodies are not specific to SLE, they are significantly associated with neuropsychiatric SLE and may represent immunological markers of psychiatric manifestations in this pathology.