Complement activation in acquired and hereditary amyloid neuropathy.
The pathogenesis of the axonal degeneration in acquired or hereditary amyloidosis is unknown. In this immunohistochemistry study, we examined 20 sural nerve biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary) for evidence of complement activation. Complement activation products were detected on and around amyloid deposits within peripheral nerves. We found no difference in the extent, location or pattern of complement activation products between the 2 forms of amyloidosis. The presence of early classical pathway activation markers in the absence of antibody in hereditary cases suggests an antibody-independent activation of the classical pathway through binding of C1q. The lack of Factor Bb-suggested alternative pathway activation was not significant in these cases. The detection of C5b-9 neoantigen on amyloid deposits demonstrated that the full complement cascade was activated. Complement activation on amyloid deposits and the generation of C5b-9 in vivo may contribute to bystander injury of axons in the vicinity of amyloid deposits.
Hafer-Macko
C E
CE
Department of Neurology, University of Maryland School of Medicine, Baltimore 21201-1595, USA. cmacko@umaryland.edu
Dyck
P J
PJ
Koski
C L
CL
D000368:Aged; D000686:Amyloidosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D001706:Biopsy; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000032:analysis / Q000276:immunology; D015933:Complement C3d / Q000032:analysis / Q000276:immunology; D003181:Complement C4 / Q000032:analysis / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000032:analysis / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013497:Sural Nerve / Q000276:immunology / Q000473:pathology
D003181:Complement C4; D015938:Complement Membrane Attack Complex; D015922:Complement C1q; D015933:Complement C3d