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1/2. Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders.

    T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4( ) and CD8( ) T cell clones through the detection and quantification of T cell receptor (TCR) alpha or beta chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders.
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2/2. A dystonic syndrome associated with anti-basal ganglia antibodies.

    Anti-basal ganglia antibodies (ABGA) have been associated with movement disorders (usually tics and chorea) and psychiatric disturbance in children. This report describes five adult and adolescent patients (one male, four females; mean age of onset, 16 years (range, 13-35)) who presented subacutely with a clinical syndrome dominated by dystonia and had ABGA binding to antigens of similar molecular weights to those seen in Sydenham's chorea. Three patients had a clear history of respiratory infection before the onset of their symptoms. Three patients received immunosuppressive treatment, with three showing a notable reduction in symptoms. It is hypothesised that dystonia in adults or adolescents may be part of the clinical spectrum of the post-infectious syndrome associated with ABGA.
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