title: Activation of the complement system in primary sclerosing cholangitis.
abstract: Recent evidence, including the presence of circulating immune complexes, suggests that abnormalities of humoral immunity may be important in the pathogenesis of primary sclerosing cholangitis. The aim of the present study was to determine whether activation of the complement system is present in patients with this disease, as this would be supportive evidence of a role for circulating immune complexes in primary sclerosing cholangitis. Plasma complement fragments C3d and C4d, and serum C3 and C4, their respective parent molecules, have been assayed. Both C3d and C4d were elevated in patients with primary sclerosing cholangitis compared with patients with extrahepatic obstructive cholestasis and normal controls (p less than 0.01 in all instances). C3 was elevated in both patient groups, in whom it was similar, compared with normal controls (p less than 0.001 in both cases), whereas C4 was similar in all groups. Elevated levels of circulating immune complexes were identified in 21 of 24 (88%) patients with primary sclerosing cholangitis, but in none of the normal controls. These findings support the hypothesis that in primary sclerosing cholangitis circulating immune complexes are associated with activation of complement via the classical pathway.
authors.affiliation: Department of Immunology, King's College School of Medicine and Dentistry, London, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Senaldi
authors.forename: P T
authors.initials: PT
authors.lastname: Donaldson
authors.forename: S
authors.initials: S
authors.lastname: Magrin
authors.forename: J M
authors.initials: JM
authors.lastname: Farrant
authors.forename: G J
authors.initials: GJ
authors.lastname: Alexander
authors.forename: D
authors.initials: D
authors.lastname: Vergani
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D000328:Adult; D000936:Antigen-Antibody Complex / Q000032:analysis; D015209:Cholangitis, Sclerosing / Q000276:immunology*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D015933:Complement C3d / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D003176:Complement C3; D003181:Complement C4; D006680:HLA Antigens; D010446:Peptide Fragments; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d