title: Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation of classical and lectin pathways.
abstract: Immune complex-mediated complement activation through the classic pathway plays a key role in the pathogenesis of lupus nephritis (LN). C4d deposition in renal tissue reflects the prognosis of systemic lupus erythematosus (SLE). The aim of the current study is to investigate the pathogenesis and clinicopathologic significance of glomerular C4d deposition in LN. We retrospectively analyzed clinical and histopathological data of 20 SLE patients with renal biopsy-proven LN and 10 non-SLE renal biopsy samples as control. LN biopsies showed varying degrees of glomerular C4d staining associated with immune complex deposits, IgG (p = 0.015), C1q (p = 0.032) and C3 (p = 0.049). 7 LN biopsies had all of C4d, C1q and C3 deposits in their glomeruli, indicative of the activation of the classical pathway, whereas 2 LN biopsies had C4d and C3 deposits without accompanying C1q deposits, indicating the activation of the lectin pathway. Glomerular C4d deposition was correlated with the LN subtype (p < 0.001). In particular, a diffusely intense and coarsely granular pattern of C4d deposition in all glomeruli was detected in class V membranous LN. However, glomerular C4d deposition was correlated with neither disease activity of SLE nor histological activity and chronicity of LN. In conclusion, the activation of the lectin pathway as well as the classical pathway seems to play a crucial role in the pathogenesis of LN. Glomerular C4d staining could be helpful for diagnosing class V membranous LN, although glomerular C4d deposition does not reflect SLE disease activity and histological activity and chronicity.
authors.affiliation: Department of Pathology, Catholic University of Daegu School of Medicine Daegu, Republic of Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Young-In
authors.initials: YI
authors.lastname: Maeng
authors.forename: Sun-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: In Hee
authors.initials: IH
authors.lastname: Lee
authors.forename: Jisuk
authors.initials: J
authors.lastname: Bae
authors.forename: Yu-Na
authors.initials: YN
authors.lastname: Kang
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Park
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D037102:Lectins / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D037102:Lectins; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: C4d; Lupus nephritis; classical pathway; disease activity; lectin pathway