Lupus nephritis: an imbalance between cytokine homeostasis and immune complex deposition. In predisposing susceptible individuals who develop systemic lupus erythematosus (SLE), there is an acquired poor clearance of apoptotic bodies and a diminished phagocytic capacity by macrophages (1). Early formation of immune complexes (ICs) include antinucleosomes, anti-double-stranded DNA (anti-dsDNA), DNA extractable nuclear antigen antibodies (ENAS), antibodies against C1q complex of the complement system, free DNA, antiribonucleoproteins (anti-RNP), and histones as byproducts of inefficient phagocytosis of apoptotic bodies (2). Circulating ICs are deposited initially at the glomerular base membrane (GBM), mesangium, and interstitial tissue within the proximal tubular epithelial cells (PTECs) (3) and (4). The deposited ICs initiate the release of proinflammatory cytokines and chemokines such as monocyte chemoattractant protein 1 (MCP-1), interleukins 1 and 6 (IL-1, IL-6) and adhesion molecules (CAMs) thus establishing a chronic inflammatory process (5). The resulting overload of the mesangial phagocytic system (innate immune system) leads to deposits of subendothelial ICs becoming an easy target for monocyte migration and infiltration and generating endothelial injury and proliferation (6) and (7). In turn, the adaptive immune system is activated secondary to the presence of ICs and dendritic cells (DCs) (8), which subsequently trigger release of type 1 interferon and induce maturation and activation of infiltrating T cells. This activation leads to sequential amplification of T helper 2 lymphocytes (Th2), T helper 1 (Th1), and T helper 17 (Th17) (9). Each of these amplifies lymphocyte B cell response and further activates macrophages, generating a second general response, which increases recruitment of effector cells that can no longer be modulated by regulatory T cells and resulting in the end in epithelial glomerular proliferation and fibrosis (10).
