Immunopathology of secondary-progressive multiple sclerosis
Version of Record online: 5 OCT 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 50, Issue 5, pages 646–657, November 2001
How to Cite
Prineas, J. W., Kwon, E. E., Cho, E.-S., Sharer, L. R., Barnett, M. H., Oleszak, E. L., Hoffman, B. and Morgan, B. P. (2001), Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol., 50: 646–657. doi: 10.1002/ana.1255
- Issue online: 25 OCT 2001
- Version of Record online: 5 OCT 2001
- Manuscript Revised: 30 JUL 2001
- Manuscript Accepted: 30 JUL 2001
- Manuscript Received: 22 MAR 2001
- Medical Research Service of the Department of Veteran Affairs
- National Multiple Sclerosis Society
Twenty-three plaques obtained at early autopsy from 2 patients with secondary-progressive multiple sclerosis were examined immunohistochemically for microglia/macrophages, and for immunoglobulins and components of activated complement. 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 engaging short segments of disrupted myelin that were associated with deposits of C3d, an opsonin formed during complement activation. Similar microglia/C3d/myelin profiles were not observed in newly forming lesions in cases of acute multiple sclerosis or other central white matter diseases. As C3d coupling is known to increase the immunogenicity of potential antigens enormously, present findings point to disrupted myelin close to plaques as a possible source of the putative multiple sclerosis antigen. Ongoing myelin destruction 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 disease progression in cases of secondary-progressive multiple sclerosis.