title: Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare.
abstract: OBJECTIVE
  Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare.
  
  
  METHODS
  Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q-positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients).
  
  
  RESULTS
  In the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P<0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare.
  
  
  CONCLUSIONS
  Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and dan.birmingham@osumc.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Birmingham
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Bitter
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.
authors.forename: Ezinne G
authors.initials: EG
authors.lastname: Ndukwe
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dials
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.
authors.forename: Terese R
authors.initials: TR
authors.lastname: Gullo
authors.affiliation: Division of Biostatistics, Ohio State University College of Public Health, Columbus, Ohio.
authors.forename: Sara
authors.initials: S
authors.lastname: Conroy
authors.affiliation: Division of Biostatistics, Ohio State University College of Public Health, Columbus, Ohio.
authors.forename: Haikady N
authors.initials: HN
authors.lastname: Nagaraja
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hebert
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015922:Complement C1q / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis; D003179:Complement C3b / Q000276:immunology*; D003181:Complement C4 / Q000032:analysis; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male
chemical_list: D001323:Autoantibodies; D003176:Complement C3; D003181:Complement C4; D007074:Immunoglobulin G; D015922:Complement C1q; D003179:Complement C3b
keywords: anti-C1q; anti-C3b; autoantibodies; complement C1q; cross-sectional studies; flare; humans; immunoglobulin G; lupus nephritis; prospective studies