RESUMO
BACKGROUND: The immune system may attack the brain and cause inflammatory disorders like multiple sclerosis (MS). On the other hand, the immune system may protect and support neurons. METHODS: There are two obstacles to study this paradox in humans. First, the target antigens in many human central nervous system (CNS) disorders are unknown. Second, it is often difficult to separate pathogenic from protective events, as well as primary from secondary phenomena. Idiopathic stiff person syndrome (SPS) circumvents the first obstacle, because most patients secrete antibodies against glutamic acid decarboxylase (GAD) 65. The immune response against glatiramer acetate (GA) may circumvent the second obstacle. Migration of activated T helper cells to the intrathecal compartment could be a common denominator in GA treatment and SPS. RESULTS: We here discuss recent results on T cells in MS and SPS, showing that GAD65-specific and GA-reactive lymphocytes in the cerebrospinal fluid are not a simple reflection of those in blood. CONCLUSION: The rules and mechanisms governing T cell selection and maintenance in the CNS may provide a key to the understanding of protective and detrimental aspects of CNS immunity.
Assuntos
Esclerose Múltipla/imunologia , Rigidez Muscular Espasmódica/imunologia , Autoanticorpos/imunologia , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Glutamato Descarboxilase/imunologia , Humanos , Ativação Linfocitária , Esclerose Múltipla/patologia , Rigidez Muscular Espasmódica/patologia , Linfócitos T/imunologiaRESUMO
BACKGROUND AND PURPOSE: Persistent intrathecal production of IgG autoantibodies against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of undetermined specificity has been reported in stiff person syndrome (SPS). METHODS: To chart the avidity and clonal patterns of GAD65 IgG, we performed scatchard plot of binding characteristics and isoelectric focusing-immunoblot of cerebrospinal fluid (CSF) and serum from five SPS patients. RESULTS: Oligoclonal GAD65 IgG bands, predominantly restricted to the IgG1 subclass, were detected in CSF and serum in all patients. The distribution of GAD65-specific IgG bands in serum and CSF revealed intrathecal synthesis of oligoclonal GAD65 IgG in all five patients, whilst radioimmunoassay demonstrated intrathecal synthesis of GAD65 IgG in four. The binding avidity of GAD65 IgG from CSF was more than 10 times higher than in serum in two of the patients but did not differ substantially in the remaining three. These differences were not related to symptom severity. The pattern of oligoclonal GAD65 IgG bands in CSF and serum in three patients examined remained unchanged for up to 7 years after symptom debut. CONCLUSION: This study confirms the persistent systemic and intrathecal production of GAD65-specific IgG in SPS, and further shows that this immune response is oligoclonal and mediated by a stable population of affinity maturated B cell clones.