title: Patients with systemic lupus erythematosus are deficient in complement-dependent prevention of immune precipitation.
abstract: OBJECTIVE
  A functional deficiency of complement has been implicated but not conclusively demonstrated in the pathogenesis of systemic lupus erythematosus (SLE). To test this, we studied several aspects of complement in 44 patients with SLE, 46 patients with rheumatoid arthritis and 102 blood donors.
  
  
  METHODS
  Prevention of immune precipitation (PIP) was measured by an enzyme immunoassay, levels of C1q, C4 and C3 by rocket immunoelectrophoresis, C4A, C4B and C3d by enzyme-linked immunosorbent assay (ELISA), complement haemolysis (CH50) by standard methods and C4 allotypes by high-voltage agarose electrophoresis and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE).
  
  
  RESULTS
  PIP was significantly reduced in SLE (P<0.001); the defect was revealed by a sensitive assay measuring this function of complement but not by the other tests employed. The patients were clinically well at the time of study, and levels of C3d, which have been shown to correlate with disease activity, were normal. The defect was more common in patients with early disease (P = 0.009), supporting a role in aetiology or early pathophysiology. PIP was positively correlated with levels of C4 (P = 3 x 10(-5)) and in particular the C4A isotype (P = 9 x 10(-10)) whereas C4B was redundant.
  
  
  CONCLUSIONS
  Our results reveal a defect in prevention of immune precipitation in SLE that is apparent at an early stage in the disease and correlates with low levels of C4A. These results indicate that subtle deficiencies of complement may predispose to SLE.
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Landspitalinn University Hospital, 101 Reykjavík, Iceland . garason@landspitali.is
authors.forename: G J
authors.initials: GJ
authors.lastname: Arason
authors.forename: K
authors.initials: K
authors.lastname: Steinsson
authors.forename: R
authors.initials: R
authors.lastname: Kolka
authors.forename: Th
authors.initials: T
authors.lastname: Víkingsdóttir
authors.forename: M S
authors.initials: MS
authors.lastname: D'Ambrogio
authors.forename: H
authors.initials: H
authors.lastname: Valdimarsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000936:Antigen-Antibody Complex / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015934:Complement C4a / Q000172:deficiency; D015941:Complement Hemolytic Activity Assay; D003165:Complement System Proteins / Q000032:analysis* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D000936:Antigen-Antibody Complex; D015934:Complement C4a; D003165:Complement System Proteins