Interactions of anti-dsDNA antibodies with human proximal renal tubular epithelial cells in the pathogenesis of lupus nephritis

2013 ◽  
Author(s):  
Sau-kwan Ho
Keyword(s):  
Epithelial Cells ◽  
Lupus Nephritis ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular ◽  
Dsdna Antibodies

Binding of anti-dsDNA antibodies to proximal tubular epithelial cells contributes to renal tubulointerstitial inflammation

2016 ◽  
Vol 131 (1) ◽  
pp. 49-67 ◽  
Author(s):  
Susan Yung ◽  
Claudia Y.C. Ng ◽  
Kin Yi Au ◽  
Kwok Fan Cheung ◽  
Qing Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lupus Nephritis ◽  
Mitogen Activated Protein Kinase ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Mapk Activation ◽  
Dsdna Antibody ◽  
Inflammatory Processes ◽  
Renal Tubular ◽  
Tubulointerstitial Inflammation

Immune deposits are often observed along the tubular basement membrane in patients with lupus nephritis, but the role of anti-dsDNA antibody (Ab) deposition on tubulointerstitial inflammation remains to be investigated. We examined the effect of human polyclonal anti-dsDNA Abs on inflammatory processes in cultured proximal renal tubular epithelial cells (PTEC, HK-2 cells) and their association with serum levels of interleukin (IL)-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in patients. Binding of anti-dsDNA Abs to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry. IL-6, IL-8 and MCP-1 secretion, mitogen-activated protein kinase (MAPK) activation and the effect of mycophenolic acid (MPA) were investigated by ELISAs and Western blot analysis. NZBWF1/J mice with active nephritis were randomized to receive either mycophenolate mofetil (MMF) (100 mg/kg per day) or vehicle for up to 12 weeks to study renal histopathology focusing on tubulointerstitial changes. Our results demonstrated that anti-dsDNA Abs bound to HK-2 cell surface and induced IL-6, IL-8 and MCP-1 secretion through distinct MAPK pathways. MPA inhibited anti-dsDNA Ab binding to HK-2 cells and suppressed apical and basolateral IL-6 and IL-8, but not MCP-1, secretion. Anti-dsDNA Ab level correlated with serum and tubulointerstitial expression of IL-6, IL-8 and MCP-1. MMF treatment in NZBWF1/J mice reduced anti-dsDNA Ab production and MAPK activation in the renal tubulointerstitium, together with decreased IL-6 and MCP-1 expression. Our data demonstrate that anti-dsDNA Abs contribute to inflammatory processes in the tubulointerstitium in lupus nephritis through their binding to proximal renal tubular epithelial cells and induction of pro-inflammatory mediators, and MPA ameliorates anti-dsDNA Ab induced IL-6 and IL-8 secretion in these cells.

scholarly journals Syndecan-1 (CD138) immunohistochemical expression patterns in lupus nephritis; reflections on different clinicopathological parameters

2020 ◽  
Vol 10 (1) ◽  
pp. e06-e06
Author(s):  
Marwa M Shakweer ◽  
Lobna S Shash
Keyword(s):  
Epithelial Cells ◽  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Urinary Albumin ◽  
Clinicopathological Parameters ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Immunohistochemical Expression ◽  
Biopsy Specimens ◽  
Renal Tubular

Introduction: Syndecan 1 (SCD1) is a lectin expressed at the surface of renal tubular epithelial cells and plasma cells. In epithelial cells, cell surface syndecan1 is cleaved by inflammation-induced proteases (eg, ADAMTS, MMP), since loss of cell surface syndecan1 is associated with higher susceptibility to cell damage. Objectives: To explore a potential additional value of SCD1 immunohistochemical expression in lupus nephritis specimens of different ISN/RPS classes and NIH activity and chronicity indices. Patients and Methods: This retrospective study included 50 renal biopsy specimens diagnosed as lupus nephritis at the pathology laboratory, and electron microscopy (EM) laboratory of Ain-Shams University specialized hospitals. Data were collected from records as personal data, medical history and laboratory results including serum creatinine and proteinuria. Immunohistochemical expression of syndecan-1 was evaluated in renal tubular epithelial cells (TECs) followed by correlation with different clinicopathological parameters. Results: Fifty renal biopsy specimens with lupus nephritis including 14 cases of class II, 4 cases of class III, 20 cases of class IV and 12 cases of class V were re-evaluated. The mean serum creatinine was 1.57 ± 0.67 mg/dL. Nine cases (18%) were negative for proteinuria, while 41 cases (82%) were presented with proteinuria with a mean of 1.5 ± 0.9 g/24 h. There was no statistically significant difference in the percentage of SCD-1 expression with different lupus classes. Serum creatinine and albumin showed a statistically significantly different correlation with semiquantitative score of SCD-1 expression. The highest value of creatinine detected with score 1 of SCD-1 expression (P=0.038) and the highest value of urinary albumin was recorded with score 1 of SCD-1 expression. Accordingly, the lowest mean of urinary albumin recorded in SCD-1 score 3 (P<0.001). There was a weekly negative association between loss of SCD-1 expression and increased NIH activity and chronicity indices. Conclusion: Loss of syndecan immunohistochemical expression in renal TECs in lupus nephritis is highly associated with proteinuria and elevated serum creatinine and can be used as a predictive marker for disease severity and progression.

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