myelin-basic-protein and Streptococcal-Infections

After implicating Streptococcus pyogenes as causing acute disseminated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptococcus contributed to the dramatic demyelination.. ADEM is a demyelinating disorder of the CNS sharing many similarities with MS. Demyelination in MS is considered to be the result of an autoimmune process mediated by autoreactive T lymphocytes with specificity for myelin antigens.. Phenotypic analysis and proliferation assays on blood monocytes, as well as isolation of myelin basic protein (MBP)-reactive T-cell lines/clones; and TCR repertorium analysis by PCR-ELISA and cytokine production.. 1) The blood T-cell receptor (TCR) repertoire was compatible with in vivo expansion induced by S. pyogenes exotoxins. 2) TCR expression analysis indicated clonal expansion of CD8+ MBP-reactive T cells, suggesting in vivo activation. MBP-reactive T cells showed crossreactivity to S. pyogenes supernatant and exotoxins. 3) Cytokine mRNA quantification of the mononuclear cells revealed a Th2-biased profile.. In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.

Topics: Autoimmunity; Brain; CD8-Positive T-Lymphocytes; Cells, Cultured; Child, Preschool; Cross Reactions; Cytokines; Encephalomyelitis, Acute Disseminated; Exotoxins; Humans; Immunophenotyping; Magnetic Resonance Imaging; Male; Myelin Basic Protein; Myelin Sheath; Quadriplegia; Streptococcal Infections; Streptococcus pyogenes; Superantigens

Topics: Amino Acid Sequence; Antigens; Bacterial Proteins; Cross Reactions; Epitopes; Genes; HLA-B27 Antigen; Humans; Klebsiella pneumoniae; Models, Biological; Myelin Basic Protein; Proteins; Streptococcal Infections