ANTISULFATIDE POLYNEUROPATHY - ANTIBODY-MEDIATED COMPLEMENT ATTACK ONPERIPHERAL MYELIN

Increased titers of circulating antisulfatide antibodies are consisten tly associated with a variety of chronic axonal and demyelinating poly neuropathy syndromes. Previous studies have shown that the pattern of antisulfatide binding to neural tissues correlates with the type of ne uropathy. This suggests a possible role for antisulfatide antibodies i n inducing peripheral nerve dysfunction, although their exact contribu tion to the pathogenesis of neuropathy is still unknown. We examined s ural nerve biopsy specimens from two patients with sensorimotor and sm all fiber sensory neuropathy associated with high titers of IgM monocl onal antibodies to sulfatide. Electrophysiological and pathological fi ndings were consistent with predominant demyelination in the patient w ith sensorimotor involvement, whereas evidence of demyelination was ob tained only by teased fiber examination in the other patient. The ultr astructural study disclosed in both cases the presence of myelinated f ibers with widely spaced myelin, due to a separation of leaflets of th e intraperiod lines. Immunocytochemistry, performed on frozen sections , demonstrated the presence of IgM and complement product C3d bound to myelin sheaths of almost all fibers. Few fibers were immunoreactive f or complement components Clq and C5. In addition, the terminal complem ent complex neoantigen C5b-C9, not associated with S protein, was dete cted on some myelinated fibers. The results suggest that, at the least in some forms of demyelinating neuropathy associated with antisulfati de antibodies, pathological changes are complement mediated. Our data further confirm previous clinical and experimental observations that c omplement activation initiates separation of myelin intraperiod lines.