Complement activation in human prion disease.
The central event in the neuropathological process of prion diseases (PrD) is the accumulation of abnormal prion protein accompanied by severe neuronal loss. Despite the infectious nature of these diseases, no prominent immune response has been detected yet. However, recent studies have shown that complement, a component of the innate immune system, is involved in the early pathogenesis of experimental prion infection. Here we demonstrate, in the diseased human brains, the presence of active compounds of the complement system, like C1q and C3b, in extracellular disease-associated prion protein deposits and the membrane attack complex in neurons. The neuronal localization of the membrane attack complex correlates well with the severity of disease-specific pathology and TUNEL labeling of neurons, irrespective of genotype or molecular phenotype of human prion diseases.
Kovacs
Gabor G
GG
Institute of Neurology, University of Vienna, Vienna, Austria.
Gasque
Philippe
P
Ströbel
Thomas
T
Lindeck-Pozza
Elisabeth
E
Strohschneider
Michaela
M
Ironside
James W
JW
Budka
Herbert
H
Guentchev
Marin
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001921:Brain / Q000276:immunology* / Q000503:physiopathology; D015922:Complement C1q / Q000276:immunology; D003179:Complement C3b / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000276:immunology*; D018620:PrPSc Proteins / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology*
D000906:Antibodies; D015938:Complement Membrane Attack Complex; D018620:PrPSc Proteins; D015922:Complement C1q; D003179:Complement C3b; D003165:Complement System Proteins