RESUMO
Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood-brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus.
Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central , Adenosina , Animais , Autoanticorpos , Autoantígenos , Guanosina , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Camundongos , RNA , ConvulsõesRESUMO
The aim of this study was to determine the role of the tumor necrosis factor like weak inducer of apoptosis (TWEAK) as a serum biomarker of neuropsychiatric involvement in systemic lupus erythematosus (NPSLE). Levels of TWEAK levels were measured in sera of 92 patients with systemic lupus erythematosus (SLE), including 28 patients with neuropsychiatric lupus, and in 59 healthy controls using ELISA. All SLE patients underwent rheumatological, neurological and psychiatric assessment. We found no significant differences in TWEAK levels, between SLE patients and the healthy controls (p=0.2411). Similarly, no difference was observed between subgroup of NPSLE and healthy controls (p=0.7658). The mean SLE disease activity (SLEDAI) was 13.25. No correlations between TWEAK levels with disease activity (SLEDAI, r=0.2113, p=0.2805) or the most common NPSLE manifestations such as headache (r=0.2079), seizures (r=0.1101), cerebrovascular disease (r= 0.2347), cognitive dysfunction (r=0.1597) and anxiety (r=0.1397) were observed. Our data do not support the use of serum TWEAK as a discriminating biomarker for NPSLE. The role of the TWEAK in NPSLE remains to be investigated.
Assuntos
Citocina TWEAK/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Ansiedade/sangue , Ansiedade/diagnóstico , Ansiedade/psicologia , Biomarcadores/sangue , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Pessoa de Meia-IdadeRESUMO
This study aimed to systematically review neuropsychiatric lupus erythematosus (NPSLE) and establish a simplified diagnostic criterion for NPSLE. Publications from 1994 to 2018 in the database (Wanfang data (http://www.wanfangdata.com.cn/index.html) and China National Knowledge Internet (http://www.cnki.net)) were included. In total, 284 original case reports and 24 unpublished cases were collected, and clinical parameters were analyzed. An attempt was made to develop a set of simplified diagnostic criteria for NPSLE based on cases described in the survey and literature; moreover, and pathophysiology and management guidelines were studied. The incidence rate of NPSLE was estimated to be 12.4% of SLE patients in China. A total of 408 NPSLE patients had 652 NP events, of which 91.2% affected the central nervous system and 8.8% affected the peripheral nervous system. Five signs (manifestations, disease activity, antibodies, thrombosis, and skin lesions) showed that negative and positive predictive values were more than 70%, included in the diagnostic criteria. The specificity, accuracy, and positive predictive value (PPV) of the revised diagnostic criteria were significantly higher than those of the American College of Rheumatology (ACR) criteria (χ2=13.642, 15.591, 65.010, p<0.001). The area under the curve (AUC) for revised diagnostic criteria was 0.962 (standard error=0.015, 95% confidence intervals [CI] =0.933-0.990), while the AUC for the ACR criteria was 0.900 (standard error=0.024, 95% CI=0.853-0.946). The AUC for the revised diagnostic criteria was different from that for the ACR criteria (Z=2.19, p<0.05). Understanding the pathophysiologic mechanisms leading to NPSLE is essential for the evaluation and design of effective interventions. The set of diagnostic criteria proposed here represents a simplified, reliable, and cost-effective approach used to diagnose NPSLE. The revised diagnostic criteria may improve the accuracy rate for diagnosing NPSLE compared to the ACR criteria.
Assuntos
Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Reumatologia , China , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: A prevailing hypothesis for neuropsychiatric involvement in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome is that brain reactive autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a role in cerebral involvement in human SLE and primary Sjögren's syndrome, and whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric manifestations. METHODS: TWEAK was measured in the cerebrospinal fluid and serum and compared with markers of blood-brain barrier permeability (Q-albumin and MRI contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE and 52 primary Sjögren's syndrome patients. Furthermore, we estimated the general intrathecal B-cell activation (IgG index), measured anti-NR2 antibodies in cerebrospinal fluid, and explored whether these variables were associated with neuropsychiatric manifestations. RESULTS: No associations were found between TWEAK in the cerebrospinal fluid or serum and neuropsychiatric manifestations in SLE nor in primary Sjögren's syndrome patients. Furthermore, no associations were found between neuropsychiatric manifestations and indicators of blood-brain barrier integrity or astroglial activity. Anti-NR2 antibodies were associated with impaired visuospatial processing (odds ratio 4.9, P = 0.03) and motor functioning (odds ratio 6.0, P = 0.006). CONCLUSION: No clinical neuropsychiatric manifestations could be attributed to impaired integrity of the blood-brain barrier, or to TWEAK levels in cerebrospinal fluid or serum in either patient group. The TWEAK concentration was considerably higher in the cerebrospinal fluid than in blood, which indicates intrathecal production. We hypothesize that increased TWEAK and S100B result from immunological stress caused by brain-reactive antibodies produced by brain residing immune cells.
Assuntos
Barreira Hematoencefálica/patologia , Citocina TWEAK/sangue , Citocina TWEAK/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Síndrome de Sjogren/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Modelos Lineares , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/psicologiaRESUMO
Abstract Aim: To investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations. Patients and methods: Sixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT-PCR). Results: Statistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p < 0.001] and GG [10% vs 66.7%, p < 0.001]). Conclusion: Polymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients.
Resumo Objetivo: Investigar a relação entre o polimorfismo genético do fator de crescimento vascular endotelial (VEGF) em pacientes com lúpus eritematoso sistêmico (LES) e manifestações neuropsiquiátricas relacionadas com o lúpus. Pacientes e métodos: Foram recrutados 60 pacientes adultos com LES nos departamentos de Reumatologia e Neurologia de hospitais universitários do Cairo e classificados em dois grupos; grupo A: 30 pacientes com manifestações neuropsiquiátricas (LESNP) e grupo B: 30 pacientes sem manifestações neuropsiquiátricas. Genotipou-se o SNP G1612A (rs10434) do gene VEGF em ambos os grupos por reação em cadeia da polimerase em tempo real (RT-PCR). Resultados: Foi encontrada diferença estatisticamente significativa nas frequências genotípicas e alélicas entre os dois grupos (AA [70% vs. 13,3%, p < 0,001] e GG [10% vs. 66,7%, p < 0,001]). Conclusão: O polimorfismo no gene que codifica o VEGF pode estar associado ao aumento na incidência de lúpus neuropsiquiátrico em pacientes com LES.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Predisposição Genética para Doença/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Projetos Piloto , Estudos Transversais , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Perfilação da Expressão Gênica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Genótipo , Pessoa de Meia-IdadeRESUMO
AIM: To investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations. PATIENTS AND METHODS: Sixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT-PCR). RESULTS: Statistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p<0.001] and GG [10% vs 66.7%, p<0.001]). CONCLUSION: Polymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients.
Assuntos
Predisposição Genética para Doença/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that can affect multiple end organs. Kidney and brain are two of the organs most commonly involved in SLE. Past studies have suggested the importance of macrophages in the pathogenesis of lupus nephritis (LN). Furthermore, as the immune effectors of the brain, microglia have been implicated in pathways leading to neuropsychiatric SLE (NPSLE). We depleted macrophages and microglia using GW2580, a small colony stimulating factor-1 receptor (CSF-1R) kinase inhibitor, in MRL-lpr/lpr (MRL/lpr) mice, a classic murine lupus model that displays features of both LN and NPSLE. Treatment was initiated before the onset of disease, and mice were followed for the development of LN and neurobehavioral dysfunction throughout the study. Treatment with GW2580 significantly ameliorated kidney disease, as evidenced by decreased proteinuria, BUN, and improved renal histopathology, despite equivalent levels of IgG and C3 deposition in the kidneys of treated and control mice. We were able to confirm macrophage depletion within the kidney via IBA-1 staining. Furthermore, we observed specific improvement in the depression-like behavioral deficit of MRL/lpr mice with GW2580 treatment. Circulating antibody and autoantibody levels were, however, not affected. These results provide additional support for the role of macrophages as a potentially valuable therapeutic target in SLE. Inhibiting CSF-1 receptor signaling would be more targeted than current immunosuppressive therapies, and may hold promise for the treatment of renal and neuropsychiatric end organ disease manifestations.
Assuntos
Anisóis/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Pirimidinas/uso terapêutico , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Animais , Anisóis/farmacologia , Anticorpos Antinucleares/imunologia , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Cromatina/imunologia , Proteínas do Sistema Complemento/imunologia , Citocinas/imunologia , Depressão/tratamento farmacológico , Depressão/imunologia , Depressão/patologia , Modelos Animais de Doenças , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Locomoção/efeitos dos fármacos , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Nefrite Lúpica/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Macrófagos/imunologia , Camundongos Endogâmicos MRL lpr , Pirimidinas/farmacologia , Memória Espacial/efeitos dos fármacosRESUMO
Neuropsychiatric manifestations are serious and frequent complications of systemic lupus erythematous (SLE). Catatonia is a neuropsychiatric disorder characterized by motor disturbance (including waxy flexibility and catalepsy), stupor, excitement, negativism, mutism, echopraxia and echolalia. Catatonia associated with SLE has been only rarely reported, especially in children. Here we present a case of a 14-year-old patient encountered in consultation-liaison psychiatry who presented catatonia associated with SLE. Her catatonia was refractory to treatment with pulse methylprednisolone, intravenous cyclophosphamide and rituximab. The patient responded to a combined therapy of electroconvulsive therapy and benzodiazepines. The present case suggests that although rarely reported, catatonia seen in the background of SLE should be promptly identified and treated to reduce the morbidity.
Assuntos
Catatonia/terapia , Eletroconvulsoterapia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Adolescente , Benzodiazepinas/uso terapêutico , Catatonia/diagnóstico , Catatonia/etiologia , Catatonia/psicologia , Terapia Combinada , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Resultado do TratamentoRESUMO
Given the early onset of neuropsychiatric disease and the potential response to immunosuppressive therapy, neuropsychiatric disease is considered a primary disease manifestation in systemic lupus erythematosus (SLE). However, the pathogenesis is not fully understood and optimal treatment has yet to be determined. TWEAK is a TNF family ligand that mediates pleotropic effects through its receptor Fn14, including the stimulation of inflammatory cytokine production by astrocytes, endothelial cells, and other non-hematopeotic cell types, and induction of neuronal death. Furthermore, TWEAK-inducible mediators are implicated in neuropsychiatric lupus. Thus, we hypothesized that the TWEAK/Fn14 pathway may be involved in the pathogenesis of neuropsychiatric SLE. We generated MRL-lpr/lpr (MRL/lpr) mice deficient for Fn14, the sole known signaling receptor for TWEAK. Neuropsychiatric disease was compared in age- and gender-matched MRL/lpr Fn14 wild type (WT) and knockout (KO) mice, using a comprehensive battery of neurobehavioral tests. We found that MRL/lpr Fn14WT mice displayed profound depression-like behavior as seen by increased immobility in a forced swim test and loss of preference for sweetened fluids, which were significantly ameliorated in Fn14KO mice. Similarly, MRL/lpr Fn14WT mice had impaired cognition, and this was significantly improved in Fn14KO mice. To determine the mechanism by which Fn14 deficiency ameliorates neuropsychiatric disease, we assessed the serum levels of autoantibodies and local expression of cytokines in the cortex and hippocampus of lupus mice. No significant differences were found in the serum levels of antibodies to nuclear antigens, or autoantibodies specifically associated with neuropsychiatric disease, between MRL/lpr Fn14WT and KO mice. However, MRL/lpr Fn14KO mice had significantly decreased brain expression of RANTES, C3, and other proinflammatory mediators. Furthermore, MRL/lpr Fn14KO mice displayed improved blood brain barrier integrity. In conclusion, several central manifestations of neuropsychiatric lupus, including depression-like behavior and altered cognition, are normalized in MRL/lpr mice lacking Fn14. Our results are the first to indicate a role for the TWEAK/Fn14 pathway in the pathogenesis of neuropsychiatric lupus, and suggest this ligand-receptor pair as a potential therapeutic target for a common and dangerous disease manifestation.
Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Receptores do Fator de Necrose Tumoral/imunologia , Fatores de Necrose Tumoral/imunologia , Animais , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Barreira Hematoencefálica/imunologia , Encéfalo/imunologia , Transtornos Cognitivos/etiologia , Citocina TWEAK , Depressão/etiologia , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Camundongos , Camundongos Endogâmicos MRL lpr , Camundongos Knockout , Neuroimunomodulação , Receptores do Fator de Necrose Tumoral/deficiência , Receptores do Fator de Necrose Tumoral/genética , Transdução de Sinais/imunologia , Receptor de TWEAK , Regulação para CimaRESUMO
BACKGROUND: The American College of Rheumatology has defined 19 neuropsychiatric syndromes associated with systemic lupus erythematosus (SLE) involving the central, peripheral, and autonomic nervous systems. Neuropsychiatric manifestations of lupus (NPSLE) have been shown to occur in up to 95% of pediatric patients with SLE. OBJECTIVE: The authors describe a 15-year-old African American young woman with a family history positive for bipolar I disorder and schizophrenia, who presented with symptoms consistent with an affective disorder. METHOD: The patient was diagnosed with Bipolar I disorder with catatonic features and required multiple hospitalizations for mood disturbance. Two years after her initial presentation, the patient was noted to have a malar rash and subsequently underwent a full rheumatologic work-up, which revealed cerebral vasculitis. RESULTS: NPSLE was diagnosed and, after treatment with steroids, the patient improved substantially and no longer required further psychiatric medication or therapy. CONCLUSION: Given the especially high prevalence of NPSLE in pediatric patients with lupus, it is important for clinicians to recognize that neuropsychiatric symptoms in an adolescent patient may indeed be the initial manifestations of SLE, as opposed to a primary affective disorder.
Assuntos
Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/psicologia , Metilprednisolona/uso terapêutico , Adolescente , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Catatonia/diagnóstico , Catatonia/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologiaRESUMO
Psychiatric manifestations are relatively common in systemic lupus erythematosus (SLE) patients. Since there are factors causing psychiatric manifestations other than SLE, the diagnosis of lupus psychosis (LP) is often difficult. Previous studies disclosed that cerebrospinal fluid (CSF) IL-6 was elevated in SLE patients with neuropsychiatric manifestation. The current studies were therefore designed to examine the efficacy of CSF IL-6 in diagnosis of LP. Multicenter retrospective study was performed with 45 SLE patients who showed psychiatric manifestations between 1993 and 2000. The diagnosis of LP and psychosis due to causes other than SLE (non-LP) was confirmed by retrospective review of the clinical records. Thirty-two of the 45 patients were reconfirmed as LP in the retrospective study. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of CSF IL-6 for diagnosis of LP were 87.5% and 92.3%, respectively, at the cut-off value of 4.3 pg/ml. These results indicate that CSF IL-6 might be an effective measure in diagnosing LP, although exclusion of infectious meningoencephalitis and cerebrovascular accident is necessary.
Assuntos
Interleucina-6/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Transtornos Mentais/diagnóstico , Valor Preditivo dos Testes , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Transtornos Mentais/líquido cefalorraquidiano , Transtornos Mentais/psicologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To define the cytokine and chemokine profile in cerebrospinal fluid (CSF) from patients with neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Forty-two SLE patients who had been hospitalized because of NP manifestations were studied. Patients were evaluated at hospitalization and 6 months later; a CSF sample was obtained at each evaluation. As controls, CSF from 6 SLE patients with septic meningitis, 16 SLE patients with no history of NP manifestations (non-NPSLE), and 25 patients with nonautoimmune diseases were also studied. Soluble molecules, including cytokines (interleukin-2 [IL-2], IL-4, IL-6, IL-10, tumor necrosis factor alpha [TNFalpha], and interferon-gamma [IFNgamma]) and chemokines (monocyte chemotactic protein 1 [MCP-1], RANTES, IL-8, monokine induced by IFNgamma [MIG], and interferon-gamma-inducible 10-kd protein [IP-10]), were measured with the use of cytometric bead array kits. RESULTS: CSF levels of the following molecules were significantly increased in NPSLE patients as compared with non-NPSLE and nonautoimmune diseases control patients, respectively: IL-6 (32.7 versus 3.0 and 2.96 pg/ml), IL-8 (102.8 versus 29.97 and 19.7 pg/ml), IP-10 (888.2 versus 329.7 [P not significant] and 133.6 pg/ml), RANTES (3.8 versus 2.5 and 2.2 pg/ml), MCP-1 (401.7 versus 257.9 [P not significant] and 136.9 pg/ml), and MIG (35.4 versus 11.4 and 3.5 pg/ml). Low levels of IL-2, IL-4, IL-10, TNFalpha, and IFNgamma were found in all groups. All cytokines and chemokines, except TNFalpha, were significantly higher among the SLE patients with septic meningitis than among the NPSLE patients. Six months later and in the absence of NP manifestations, all elevated molecule levels, except RANTES, in patients with NPSLE had decreased significantly, and no differences were noted between the NPSLE and non-NPSLE groups. CONCLUSION: A central nervous system response composed of IL-6 and chemokines, but not Th1/Th2 cytokines, is associated with NP manifestations in SLE patients.
Assuntos
Quimiocinas/líquido cefalorraquidiano , Interleucina-6/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Adulto , Citocinas/líquido cefalorraquidiano , Feminino , Humanos , Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Índice de Gravidade de DoençaRESUMO
Growing evidence suggests that autoantibodies to neuronal or endothelial targets in psychiatric disorders exist and may be pathogenic. This review describes and discusses the possible role of autoantibodies related to the psychiatric manifestations in autoimmune diseases, autoantibodies related to the psychiatric disorders present in post-streptococcal diseases, celiac disease, chronic fatigue syndrome and substance abuse, and autoantibodies related to schizophrenia and autism, disorders now considered of autoimmune origin.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Encéfalo/imunologia , Transtornos Mentais/imunologia , Transtorno Autístico/imunologia , Transtorno Autístico/fisiopatologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Encéfalo/fisiopatologia , Doença Celíaca/complicações , Doença Celíaca/imunologia , Doença Celíaca/fisiopatologia , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/fisiopatologia , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Transtornos Mentais/fisiopatologia , Esquizofrenia/imunologia , Esquizofrenia/fisiopatologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/imunologiaRESUMO
OBJECTIVE: To determine the factors associated with seizures in systemic lupus erythematosus (SLE). METHODS: One hundred ninety-five patients with SLE were followed at the University of Maryland Lupus Clinics from January 1992 until June 2004. Neuropsychiatric (NP) manifestations were defined according to the American College of Rheumatology nomenclature and case definitions for NP-SLE syndromes, and seizures were defined using the International Classification of Epileptic Seizures. At the end of the study period, 28 of the 195 (14%) patients with SLE had seizures (21 generalized convulsive, 7 partial) during their course of disease. Recurrent seizures or epilepsy occurred in 12 of 28 patients (43%). The baseline features of those patients with seizures and those without them were compared to determine their contribution to the occurrence of isolated seizures and epilepsy. RESULTS: Isolated seizures in SLE are common; epilepsy is less frequent but nonetheless important. Certain clinical features at baseline were independent predictors of seizures including disease activity, in particular psychosis, moderate- to high-titer serum anti-cardiolipin and anti-Smith antibodies, and damage accrual. Higher disease activity at baseline, concurrent multiple NP-SLE manifestations, prior strokes, and male gender were predictive of epilepsy. CONCLUSION: The risk of seizure and epilepsy in systemic lupus erythematosus (SLE) is increased in those patients with higher disease activity at baseline, prior neuropsychiatric SLE disease, and anti-cardiolipin and anti-Smith antibodies.
Assuntos
Encéfalo/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Autoanticorpos/sangue , Autoantígenos , Cardiolipinas/imunologia , Estudos de Coortes , Progressão da Doença , Epilepsia/psicologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Transtornos Psicóticos/complicações , Análise de Regressão , Ribonucleoproteínas Nucleares Pequenas/imunologia , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/complicações , Proteínas Centrais de snRNPRESUMO
Neuropsychiatric manifestations are relatively common and serious complications in systemic lupus erythematosus (CNS lupus). Overall, in patients with CNS lupus, CSF IgM, IgA, IgG indexes (indicators of intrathecal Ig synthesis) as well as CSF IL-6 activities were significantly elevated. Of note, especially in patients lupus psychosis, but not in those with focal CNS lesions, anti-ribosomal P antibody (anti-P) in the sera as well as anti-neuronal antibody (anti-N) in the CSF was significantly elevated in relation to their CNS disease activities. These data indicate that the immune system activation within the CNS, possibly resulting in the elevation of CSF anti-N, plays an important role in the pathogenesis of CNS lupus, including lupus psychosis. CNS involvement in Behçet's disease, usually called neuro-Behçet's syndrome (NB), includes acute type and chronic progressive type. Acute NB is characterized by acute meningoencephalitis with focal lesions, presenting high intensity areas in T2-weightened images or Flare images on MRI scans, whereas chronic progressive NB is characterized by intractable slowly progressive dementia, ataxia and dysarthria with persistent elevation of CSF IL-6 activity. Chronic progressive NB is resistant to conventional treatment with steroid, cyclophosphamide, or azathioprine, but responds to low dose methotrexate. As for ANCA-related vasculitis, pachymeningitis has been found to be associated with P-ANCA as well as C-ANCA.
Assuntos
Doenças do Tecido Conjuntivo/complicações , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Anticorpos Anticitoplasma de Neutrófilos/análise , Autoanticorpos/análise , Síndrome de Behçet/etiologia , Síndrome de Behçet/patologia , Feminino , Humanos , Interleucina-6/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Meningite/etiologia , Meningite/patologia , Proteínas Ribossômicas/imunologiaRESUMO
We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.