title: Prospective assessment of C4d deposits on circulating cells and renal tissues in lupus nephritis: a pilot study.
abstract: Complement activation plays a key role in the pathogenesis of lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE). We prospectively evaluated 15 LN subjects and two control groups: 13 non-SLE renal subjects (control A) and 239 SLE subjects without LN (control B). All had C4d levels on circulating erythrocytes (E-C4d), reticulocytes (R-C4d) and platelets (P-C4d) measured by flow cytometry, while C4d deposition in renal tissue was semiquantitatively assessed in LN subjects and control A using immunoperoxidase staining. Compared with control A, LN biopsies had higher glomerular-C4d scores (p = 0.003), which were associated with more frequent granular glomerular immunofluorescence staining and electron dense deposits (p < 0.001). Compared with control A and B groups, LN subjects had higher E-C4d (p = 0.002 and p = 0.005) and R-C4d levels (p = 0.002 and p = 0.008), respectively. LN subjects were more likely to have P-C4d compared with control A (p = 0.016). In LN, only E-C4d correlated with National Institutes of Health (NIH) activity index (r = 0.55, p = 0.04). In conclusion, LN biopsies showed frequent glomerular-C4d staining associated with immune complex deposits. LN subjects had higher E-C4d and R-C4d levels compared with both control groups. E-C4d levels also correlated with NIH activity index. These findings suggest a potential role of C4d on circulating cells as a biomarker for lupus nephritis.
authors.affiliation: Department of Pathology, University of Pittsburgh, PA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Batal
authors.forename: K
authors.initials: K
authors.lastname: Liang
authors.forename: S
authors.initials: S
authors.lastname: Bastacky
authors.forename: L P
authors.initials: LP
authors.lastname: Kiss
authors.forename: T
authors.initials: T
authors.lastname: McHale
authors.forename: N L
authors.initials: NL
authors.lastname: Wilson
authors.forename: B
authors.initials: B
authors.lastname: Paul
authors.forename: A
authors.initials: A
authors.lastname: Lertratanakul
authors.forename: J M
authors.initials: JM
authors.lastname: Ahearn
authors.forename: S M
authors.initials: SM
authors.lastname: Manzi
authors.forename: A H
authors.initials: AH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000473:pathology*; D015331:Cohort Studies; D015935:Complement C4b / Q000276:immunology*; D004912:Erythrocytes / Q000473:pathology*; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008181:Lupus Nephritis / Q000097:blood* / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D010865:Pilot Projects; D011446:Prospective Studies; D012156:Reticulocytes / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d