Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy.
The localization, mode of action, and roles of complement in the Guillain-Barre syndrome have been controversial. We used high-resolution immunocytochemistry to localize complement activation products in early stages of the acute inflammatory demyelinating polyneuropathy (AIDP) pattern of Guillain-Barre syndrome. Three AIDP subjects who were autopsied had had symptoms for 3 to 9 days at the time of death. Immunocytochemistry was performed on etched, epoxy resin-embedded sections, and the next thin section was compared by electron microscopy (thick/thin sections). Many fibers had a rim of the complement activation marker C3d and the terminal complement complex neoantigen C5b-9 along the outer surface of the Schwann cells. Ultrastructural analysis of these C3d-positive fibers showed mild vesicular changes of the outermost myelin lamellae. Vesicular degeneration was seen before the invasion of macrophages into the myelin, and was the predominant change in the subject with symptoms for 3 days. C3d staining was not found on myelin membranes. The results suggest that at least some forms of AIDP are complement mediated. We speculate that complement is activated by antibody bound to epitopes on the outer surface of the Schwann cell and that the resulting complement activation initiates the vesiculation of myelin.
Hafer-Macko
C E
CE
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Sheikh
K A
KA
Li
C Y
CY
Ho
T W
TW
Cornblath
D R
DR
McKhann
G M
GM
Asbury
A K
AK
Griffin
J W
JW
D000208:Acute Disease; D001344:Autopsy; D015415:Biomarkers; D002462:Cell Membrane / Q000276:immunology / Q000648:ultrastructure; D002648:Child; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000737:chemistry / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology; D009412:Nerve Fibers / Q000737:chemistry / Q000276:immunology; D011129:Polyradiculoneuropathy / Q000276:immunology* / Q000473:pathology; D012583:Schwann Cells / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D013126:Spinal Nerve Roots / Q000166:cytology / Q000276:immunology / Q000648:ultrastructure
D015415:Biomarkers; D008565:Membrane Proteins; D003165:Complement System Proteins