Circulating cytotoxic immune components in dominant Charcot-Marie-Tooth syndrome.

Activated T cells, measured repeatedly in the demyelinating peripheral neuropathy, Charcot-Marie-Tooth syndrome (CMT; hereditary motor sensory neuropathy), might participate in myelin loss by a destructive inflammatory autoimmune process. To explore this possibility, plasma proportions of hydroxyleukotrienes, their fatty acid precursor, arachidonic acid, and lymphocyte epitopes associated with immune cell activation expression were measured in 18 adults with dominant, Type I CMT. Compared to age-matched normal controls, CMT I patients showed eicosanoid-linked immunoactivation by an elevated content of 12-hydroxy-eicosatetraenoic acid (12-HETE) in parallel with a decreased plasma percentage of its fatty acid precursor, arachidonic acid. CMT patients also had increased numbers of peripheral lymphocytes expressing activation-related epitopes, CD25+, CD26+, CD4+, and CD4/CD45RO+ primed memory cells, with enhanced CD8+ cytotoxic cells and soluble CD8 protein content. Therefore, endogenously stimulated CMT I lymphocytes include functional cytotoxic cells which appear to deplete the plasma fatty acid precursor of prostenoid agents during the secretion of potentially destructive cytokines.