title: Reduction in erythrocyte-bound complement activation products and titres of anti-C1q antibodies associate with clinical improvement in systemic lupus erythematosus.
abstract: BACKGROUND
  The relationship between cell-bound complement activation products (CB-CAPs: EC4d, EC3d), anti-C1q, soluble complement C3/C4 and disease activity in systemic lupus erythematosus (SLE) was evaluated.
  
  
  METHODS
  Per protocol, at baseline all SLE subjects enrolled in this longitudinal study presented with active disease and elevated CB-CAPs. At each monthly visit, the non-serological (ns) Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG)-2004 index scores were determined as was a random urinary protein to creatinine ratio (uPCR). Short-form 36 (SF-36) questionnaires were also collected. All soluble markers were determined using immunoassays, while EC4d and EC3d were determined using flow cytometry. Statistical analysis consisted of linear mixed models with random intercept and fixed slopes.
  
  
  RESULTS
  A total of 36 SLE subjects (mean age 34 years; 94% female) were enrolled and evaluated monthly for an average 11 visits per subject. Clinical improvements were observed during the study, with significant decreases in ns-SELENA-SLEDAI scores, BILAG-2004 index scores and uPCR, and increases in all domains of SF-36 (p<0.01). The longitudinal decrease in ns-SELENA-SLEDAI and BILAG-2004 index scores was significantly associated with reduced EC4d and EC3d levels, reduced anti-C1q titres and increased serum complement C3/C4 (p<0.05). The changes in uPCR significantly correlated with C3, C4, anti-C1q and EC4d, with EC4d outperforming C3/C4 by a multivariate analysis. The reduced EC4d or EC3d was associated with improvements in at least six out of the eight domains of SF-36 and outperformed C3/C4. Anti-dsDNA titres did not correlate with changes in disease activity.
  
  
  CONCLUSIONS
  These data indicate that CB-CAPs and anti-C1q are helpful in monitoring patients with SLE.
authors.affiliation: NYU School of Medicine , New York, New York , USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Buyon
authors.affiliation: Hofstra Northwell School of Medicine , New York, New York , USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Furie
authors.affiliation: Albert Einstein College of Medicine and Montefiore Medical Center , Bronx, New York , USA.
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
authors.affiliation: Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.affiliation: UCSD School of Medicine , La Jolla, California , USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kalunian
authors.affiliation: Exagen Diagnostics , Vista, California , USA.
authors.forename: Derren
authors.initials: D
authors.lastname: Barken
authors.affiliation: Exagen Diagnostics , Vista, California , USA.
authors.forename: John
authors.initials: J
authors.lastname: Conklin
authors.affiliation: Exagen Diagnostics , Vista, California , USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Dervieux
keywords: Disease Activity; Systemic Lupus Erythematosus; Treatment