RESUMO
Although systemic lupus erythematosus (SLE) is usually evaluated with regard to autoimmune reactivity toward the kidney, there are multiple psychiatric abnormalities associated with this autoimmune disease. Lupus-prone male NZM88 mice, derived from NZB/NZW F1 mice, develop early neuropsychiatric manifestations without any signs of nephritis. In addition to the usual repertoire of antibody specificities, including autoantibodies to dsDNA and renal antigens, mice of this inbred strain express autoantibodies to numerous brain antigens. Here, we show that autoantibodies to brain antigens, assessed by Western analysis, are as individually varied as are the diverse neuropsychiatric manifestations observed in SLE patients. Additionally, a monoclonal antibody derived from the spleen of an untreated NZM88 male when injected into healthy BALB/cByJ, but not C57BL/6J, mice induced behaviors similar to those of lupus-prone NZM88 mice. This monoclonal antibody, which is specific to dynamin-1, binds preferentially in BALB/cByJ cortex and induces substantial expression of cytokines mainly in the hypothalamus. Thus, an antibody to just one brain antigen can induce multiple behavioral changes, and multiple autoantibodies to different brain antigens exist in lupus-prone mice; however, susceptibility to the induction of neurobehavioral deficits is dependent on host genetics.
Assuntos
Anticorpos Monoclonais/imunologia , Comportamento Animal , Lúpus Vulgar/complicações , Lúpus Vulgar/imunologia , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/etiologia , Animais , Autoanticorpos/sangue , Autoantígenos/imunologia , Western Blotting , Encéfalo/imunologia , Encéfalo/metabolismo , Citocinas/biossíntese , Dinamina I/imunologia , Feminino , Predisposição Genética para Doença , Hipotálamo/metabolismo , Lúpus Vulgar/genética , Lúpus Vulgar/psicologia , Masculino , Transtornos Mentais/genética , Camundongos , Camundongos Endogâmicos/genética , Camundongos Mutantes , Doenças do Sistema Nervoso/genética , Especificidade da Espécie , Baço/imunologiaAssuntos
Dermatologia , Exposições como Assunto , Lúpus Vulgar , Fototerapia , Fisiologia , Saúde Pública , Dermatologia/educação , Dermatologia/história , História da Medicina , História do Século XIX , História do Século XX , Lúpus Vulgar/etnologia , Lúpus Vulgar/história , Lúpus Vulgar/psicologia , Paris/etnologia , Fototerapia/economia , Fototerapia/história , Fototerapia/psicologia , Fisiologia/educação , Fisiologia/história , Saúde Pública/economia , Saúde Pública/educação , Saúde Pública/história , Pesquisa/educação , Pesquisa/história , Ciência/educação , Ciência/históriaRESUMO
OBJECTIVE: To compare the role of antibodies against the ribosomal P protein (anti-P) with that of antibodies against neuronal cells (anti-N) in the pathogenesis of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34 with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF) from 41 patients with CNS lupus and from the 20 control patients were assayed for IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were significantly elevated in patients with lupus psychosis compared with those with non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no significant differences in serum anti-N levels among these 3 groups. In contrast, CSF anti-N levels were significantly elevated in patients with lupus psychosis compared with those with nonpsychotic CNS lupus and compared with non-SLE controls, whereas CSF anti-P were not detected in most of the patients. CONCLUSION: The results indicate that anti-P in the systemic circulation and anti-N in the CSF are involved in the development of lupus psychosis.