Antibodies in patients with neuropsychiatric systemic lupus erythematosus.
OBJECTIVE
To investigate a target for antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).


BACKGROUND
Pathogenesis of NPSLE may be related to autoantibody-mediated neural dysfunction, vasculopathy, and coagulopathy. However, very few autoantibodies are sensitive and specific to NPSLE because the neuropsychiatric syndromes associated with SLE are diverse in cause and presentation.


METHODS
We identified antibodies against brain antigens in the sera of 7 patients with NPSLE and 12 healthy controls by 2-dimensional electrophoresis, followed by Western blotting and liquid chromatography-tandem mass spectrometry (LC-MS/MS), using rat brain proteins as the antigen source.


RESULTS
Six antibodies were detected in patients with NPSLE. One of these 6 antibodies was found in antibodies against Rab guanosine diphosphate dissociation inhibitor alpha (alphaGDI) (which is specifically abundant in neurons and regulates synaptic vesicle exocytosis) in patients with NPSLE with psychosis. We tested more samples by 1-dimensional immunoblotting of human recombinant alphaGDI. Positivity of the anti-alphaGDI antibody was significantly higher in patients with NPSLE with psychosis (80%, 4 of 5) than in patients with NPSLE without psychosis (0%, 0 of 13), patients with systemic lupus erythematosus without neuropsychiatric symptoms (5.3%, 1 of 19), patients with multiple sclerosis (0%, 0 of 12), patients with infectious meningoencephalitis (0%, 0 of 13), patients with polyneuropathy (0%, 0 of 10), patients with psychotic syndromes (0%, 0 of 10), and healthy controls (0%, 0 of 12).


CONCLUSIONS
We propose that the anti-Rab guanosine diphosphate dissociation inhibitor alpha antibody is a candidate for further exploration as diagnostic marker of psychosis associated with neuropsychiatric systemic lupus erythematosus.
Kimura
A
A
Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. kimura1@gifu-u.ac.jp
Kanoh
Y
Y
Sakurai
T
T
Koumura
A
A
Yamada
M
M
Hayashi
Y
Y
Tanaka
Y
Y
Hozumi
I
I
Takemura
M
M
Seishima
M
M
Inuzuka
T
T
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D005089:Exocytosis / Q000276:immunology; D005260:Female; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000276:immunology; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000276:immunology; D011618:Psychotic Disorders / Q000097:blood / Q000209:etiology / Q000276:immunology*; D013572:Synaptic Vesicles / Q000276:immunology; D053719:Tandem Mass Spectrometry
D001323:Autoantibodies; D015415:Biomarkers; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors