IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 2013;6(10):2157-2167

Original Article
Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation
of classical and lectin pathways

Min-Kyung Kim, Young-In Maeng, Sun-Jae Lee, In Hee Lee, Jisuk Bae, Yu-Na Kang, Byung-Tae Park, Kwan-Kyu Park

Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea; Department of Internal Medicine, Catholic
University of Daegu School of Medicine, Daegu, Republic of Korea; 3Department of Preventive Medicine, Catholic University of Daegu School of
Medicine, Daegu, Republic of Korea; Department of Pathology, Keimyung University School of Medicine, Republic of Korea; Department of
Microbiology, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea

Received August 13, 2013; Accepted August 28, 2013; Epub September 15, 2013; Published October 1, 2013

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. (IJCEP1308030).

Keywords: Lupus nephritis, C4d, classical pathway, lectin pathway, disease activity

Address correspondence to: Dr. Kwan-Kyu Park, Department of Pathology, Catholic University of Daegu School of Medicine, 3056-6
Daemyung-4 Dong, Nam-gu, Daegu, 705-718, Republic of Korea. Tel: 82-53-650-4149; Fax: 82-53-650-3050; E-mail: kkpark@cu.ac.kr; Dr.
Byung-Tae Park, Department of Microbiology, Catholic University of Daegu School of Medicine, 3056-6 Daemyung-4 Dong, Nam-gu, Daegu,
705-718, Republic of Korea. Tel: 82-53-650-4476; Fax: 82-53-621-4106; E-mail: btpark@cu.ac.kr