title: Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus.
abstract: OBJECTIVE
  C4-derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte-bound C4 (E-C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement-bearing immune complexes via erythrocytes expressing complement receptor 1 (CR1). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E-C4 and E-CR1 expression on erythrocytes of patients with SLE.
  
  
  METHODS
  We conducted a cross-sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1.
  
  
  RESULTS
  Patients with SLE had higher levels of E-C4d and lower levels of E-CR1 than did patients with other diseases (P < or = 0.001) or healthy controls (P < or = 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%.
  
  
  CONCLUSIONS
  This is the first report of abnormal levels of E-C4d in human disease. We found that abnormally high levels of E-C4d and low levels of E-CR1 are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E-C4d/E-CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis.
authors.affiliation: University of Pittsburgh School of Medicine and Graduate School of Public Health, S722 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA 15261, USA. sxm6@pitt.edu
authors.forename: Susan
authors.initials: S
authors.lastname: Manzi
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: Navratil
authors.forename: Margie J
authors.initials: MJ
authors.lastname: Ruffing
authors.forename: Chau-Ching
authors.initials: CC
authors.lastname: Liu
authors.forename: Natalya
authors.initials: N
authors.lastname: Danchenko
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Nilson
authors.forename: Shanthi
authors.initials: S
authors.lastname: Krishnaswami
authors.forename: Dale E S
authors.initials: DE
authors.lastname: King
authors.forename: Amy H
authors.initials: AH
authors.lastname: Kao
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Ahearn
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015935:Complement C4b; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011951:Receptors, Complement / Q000097:blood*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011951:Receptors, Complement; D015935:Complement C4b; C032261:complement C4d