Review Article

Autoantibodies and Resident Renal Cells in the Pathogenesis of Lupus Nephritis: Getting to Know the Unknown

Table 2

Binding of anti-dsDNA antibodies to resident renal cells and the effect on cellular functions.

Mesangial cellsEndothelial cellsProximal renal tubular epithelial cells

Mechanism of bindingIndirect binding throughIndirect binding throughIndirect binding through
DNA, histones, and nucleosomesDNA, histones, and nucleosomesDNA
Cross-reactive binding toCross-reactive binding toCross-reactive binding to
heparan sulfatehevinA and D snRNP proteins
ribosomal P protein unidentified proteins with M.W.
lamininof 30–35, 44, 68, 110, and 180 kDa
α-actinin
annexin II
Internalization of anti-dsDNAOccurs after binding to annexin IIOccurs after binding to fibronectinOccurs after binding to
antibodies into resident renal cellsunidentified protein(s)
Effect on cell proliferationIncreaseIncreaseIncrease
Induction of apoptosisYesYesYes
Effect on cell viabilityDecreaseDecreaseDecrease
Effect on inflammationIncreased synthesis of:Increased synthesis of:Increased synthesis of:
IL-1β, IL-6, and TNF-αIL-1β, IL-6, and IL-8IL-1β
hyaluronanadhesion moleculesIL-6
von Willebrand factorTNF-α
Effect on fibrosisActivation of PKC-α, -βI,Increased gene expressionInduced epithelial-to
and βII signaling pathwaysof TGF-β1mesenchymal
and increased synthesis oftransdifferentiation
TGF-β1 and fibronectin