J Rheum Dis.  2018 Apr;25(2):81-99. 10.4078/jrd.2018.25.2.81.

Wolves Trapped in the NETs–The Pathogenesis of Lupus Nephritis

• Kim Y
• Shim SC

• KMID: 2408926
• DOI: http://doi.org/10.4078/jrd.2018.25.2.81

Abstract

Systemic lupus erythematous (SLE) is a systemic autoimmune disease with multi-organ inflammation caused by the production of pathogenic autoantibodies and immune complexes reflecting a global loss of tolerance. Lupus nephritis (LN) is present in approximately 60% of SLE patients and is considered a major predictor of a poor prognosis. To date, many studies utilizing genomics, transcriptomics, epigenetics, metabolomics, and microbiome have been conducted on a range of animal models and lupus patients to understand the pathogenesis of SLE and LN. Collectively, these studies support the concept that LN is caused by increased cell death, which has not been properly dealt with; abnormal innate immunity; hyperactive adaptive immunity; and genetic variants triggered by a range of environmental factors. This review summarizes the results from studies that contributed strongly to elucidating the pathogenesis of SLE and LN, highlighting the immunological and non-immunological mechanisms.

Keyword

Lupus nephritis; Apoptosis; Autoimmune diseases; Immunology; Lymphocytes

MeSH Terms

Adaptive Immunity
Allergy and Immunology
Antigen-Antibody Complex
Apoptosis
Autoantibodies
Autoimmune Diseases
Cell Death
Epigenomics
Genomics
Humans
Immunity, Innate
Inflammation
Lupus Nephritis*
Lymphocytes
Metabolomics
Microbiota
Models, Animal
Prognosis
Wolves*
Antigen-Antibody Complex
Autoantibodies

Figure

• 

  Figure 1 Overall pathogenic mechanism of lupus nephritis. HLA: human leukocyte antigen, SLC5A11: solute carrier family 5 member 11, PDGF: platelet-derived growth factor, TNFSF4: tumor necrosis factor ligand superfamily, member 4, ITGAM: integrin alpha M, STAT: signal transducer and activator of transcription, UV: ultraviolet, RNA: ribonucleic acid, DNA: deoxyribonucleic acid, DNase: deoxyribonuclease, pDC: plasmacytoid dendritic cells, TLR: toll-like receptor, STING: stimulator of interferon gene, IFN: interferon, TNF: tumor necrosis factor, IL: interleukin, BAFF: B cell-activating factor, CCL2: chemokine ligand 2, FGF: fibroblast growth factor, Th: helper T cells, Treg: regulatory T cells, TfH: follicular helper T cells, dsDNA: double strand DNA.

• 

  Figure 2 Potential role of aberrant cell death in the development of systemic lupus erythematous. CRP: C-reactive protein, PTX: pentraxin-related protein, DNase: deoxyribonuclease, NET: neutrophil extracellular trap, DNA: deoxyribonucleic acid, RNA: ribonucleic acid, AMP: adenosine monophosphate, HMGB1: high-mobility group box 1 protein, pDC: plasmacytoid dendritic cells, TLR: toll-like receptor, STING: stimulator of interferon gene, IFN: interferon, Th: helper T cells, Treg: regulatory T cells, TfH: follicular helper T cells.

• 

  Figure 3 Innate and acquired immunity processes contribute to systemic lupus erythematous. pDC: plasmacytoid dendritic cells, TLR: toll-like receptor, STING: stimulator of interferon gene, IFN: interferon, TNF: tumor necrosis factor, IL: interleukin, BAFF: B cell-activating factor, Treg: regulatory T cells, Th: helper T cells, TfH: follicular helper T cells.

• 

  Figure 4 Associated genes and environmental factors with the pathogenesis of systemic lupus erythematous. CRP: C-reactive protein, ATG5: α-glucoside transporter 5, TREX1: three prime repair exonuclease 1, UV: ultraviolet, HLA: human leukocyte antigen, FCGR: Fcγ receptor, IRAK: interleukin 1 receptor associated kinase, IRF: IFN regulatory factor, STAT: signal transducer and activator of transcription, ITGAM: integrin α M, TNFAIP: TNF α-induced protein, IFI27: interferon α-inducible protein 27, IFI44L: interferon-induced protein 44-like, LY6E: lymphocyte antigen 6 complex, locus E, IFITM1: interferon induced transmembrane protein 1, BANK1: B cell scaffold protein with ankyrin repeats 1, BLK: B lymphoid tyrosine kinase, ETS1: ETS proto-oncogene 1, PTPN22: protein tyrosine phosphatase, nonreceptor type 22, TNFSF: tumor necrosis factor ligand superfamily, member, IKZF1: IKAROS family zinc finger 1, SLC5A11: solute carrier family 5 member 11, PDGFR: platelet-derived growth factor receptor, NCF1: neutrophil cytosolic factor 1, ACP5: acid phosphatase 5, PRDM1: PR domain zinc finger protein 1.

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