Immunopathology of secondary-progressive multiple sclerosis

Twenty-three plaques obtained at early autopsy from 2 patients with seconda ry-progressive multiple sclerosis were examined immunohistochemically for m icroglia/macrophages, and for immunoglobulins and components of activated c omplement. Most of the lesions examined in both cases exhibited evidence of low-grade active demyelination of an unusual type (frustrated phagocytosis ) in periplaque white matter. This included linear groups of microglia enga ging short segments of disrupted myelin that were associated with deposits of C3d, an opsonin formed during complement activation. Similar microglia/C 3d/myelin profiles were not observed in newly forming lesions in cases of a cute multiple sclerosis or other central white matter diseases. As C3d coup ling is known to increase the immunogenicity of potential antigens enormous ly, present findings point to disrupted myelin close to plaques as a possib le source of the putative multiple sclerosis antigen. Ongoing myelin destru ction found in a high proportion of old, established plaques was surprising . It suggests that slowly expanding lesions (progressive plaques), in which ongoing myelin breakdown occurs in the absence of florid perivascular cell cuffing or other histological signs of acute inflammation, contribute to d isease progression in cases of secondary-progressive multiple sclerosis..