The pathogenesis of lupus nephritis - PubMed (original) (raw)

Figure 1.

Pathomechanisms of LN outside the kidney. (A) Genetic variants of homeostatic cell death (i.e., Fas variants) and the rapid clearance of dead cell corpses (e.g., C3/4 variants or DNAses variants) result either in secondary necrosis or incomplete chromatin digestion, which both promote the exposure of nuclear particles to the immune system. (B) Nuclear particles resemble viral particles and activate the same viral nucleic acid recognition receptors on antigen-presenting cells. Genetic variants of those signaling elements are recognized to be risk factors for SLE. The activation of antigen-presenting cells changes (by costimulation) the immune interpretation of concomitantly presented antigens of the same particle. (C) Polyclonal lymphocyte expansion has multiple effects on the disease process and genetic variants further affect the differentiation of T helper cells. The complex regulation of lymphocyte activation and expansion is affected by multiple genetic variants. The susceptibility genes and genes/molecules that are involved within each biologic pathway are listed to the right: C1q, C2, C4A/B, C-reactive protein (CRP), α-glucoside transporter 5 (ATG5), three prime repair exonuclease 1 (TREX1), B cell CLL/lymphoma 2 (Bcl-2), IL-2 receptor α (IL-2Rα), tyrosine-protein kinase receptor 3 (TYRO3), mast/stem cell growth factor (MGF), Fcγ receptor (FcGR), HLA IL-1 receptor–associated kinase (HLA IRAK), IFN regulatory factor (IRF), signal transducer and activator of transcription (STAT), integrin αM (ITGAM), TNF α-induced protein 3 (TNFAIP3), zinc finger protein 36 (Zfp-36), IL-4, IFN-γ, MHCI, MHCII, TNF, TLR7, single Ig and Toll-IL 1 receptor (SIGIRR), B cell scaffold protein with ankyrin repeats 1 (BANK1), B lymphoid tyrosine kinase (BLK), IKAROS family zinc finger 1 (IKZF1), protein tyrosine phosphatase, nonreceptor type 22 (PTPN22), pituitary tumor-transforming 1 (PTTG1), RAS guanyl releasing protein 3 (RASGRP3), TNF (ligand) superfamily, member 4 (TNFSF4), TNFAIP3-interacting protein 1 (TNIP1), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), BAFF/BLyS, cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1/PDCD-1), and Gadd45 (activated by the stress-inducible GADD45).