Immunological pathogenesis and treatment of systemic lupus erythematosus

Abstract

Background: Systemic lupus erythematosis (SLE) is a complex and clinically heterogeneous autoimmune disease. A variety of immunological defects contribute to SLE, including dysregulated innate and adaptive immune response. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment. The aim of this review was to clarify the immunological pathogenesis and treatment of SLE.

Data sources: Literature reviews and original research articles were collected from database, including PubMed and Wanfang. Relevant articles about SLE were included.

Results: Breakdown of self-tolerance is the main pathogenesis of SLE. The innate and adaptive immune networks are interlinked with each other through cytokines, complements, immune complexes and kinases of the intracellular machinery. Treatments targeted at possible targets of immunity have been assessed in clinical trials. Most of them did not show better safety and efficacy than traditional treatments. However, novel targeting treatments are still being explored.

Conclusions: Dysregulated immune response plays a critical role in SLE, including innate immunity and adaptive immunity. Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.

Keywords: Immunological pathogenesis; Systemic lupus erythematosis; Treatment.

Fig. 1

Pattern recognition receptors play a vital role in the innate immunity in lupus. PRRs pattern recognition receptors, NLR nucleotide binding and oligomerization domain receptors, TLR toll-like receptor, RLR retinoid acid inducible gene-I-like receptors, DC dendritic cell, BCR B-cell receptor, FcR fragment crystallizable receptor, NALP1 NAcht leucine-rich-repeat protein 1, AIM2 absent in melanoma 2, ASC apoptotic speck-like protein containing a caspase recruitment domain, IFN interferon, IL interleukin

Fig. 2

T-cell signaling alteration in systemic lupus erythematosus (SLE). TCR T cell receptor, Lck lymphocyte-specific protein tyrosine kinase, ZAP-70 zeta-chain-associated protein kinase 70, FcRγ Fc receptor common gamma subunit chain, Syk Spleen tyrosine kinase, NFAT nuclear factor of activated T cells, CaMKIV activated calmodulin kinase IV, CREM cAMP responsive element modulator, IL interleukin, PIP2 phosphatidylinositol-4, 5-bisphosphate, PIP3 phosphatidylinositol-3, 4, 5-triphosphate, PI3K phosphoinositide-3 kinase, Akt protein kinase B, mTORC mammalian target of rapamycin complex, ERM ezrin/radixin/moesin, ROCK Rho-associated protein kinase

Fig. 3

Classic T–B cells interactions in SLE. BCR B-cell receptor, TLR Toll-like receptor, MHC-II major histocompatibility complex-II, BCL B-cell lymphoma, ICOS inducible co-stimulator, ICOSL inducible co-stimulator ligand, TCR T cell receptor, IL interleukin, IgM immunoglobulin M, IgG immunoglobulin G, BAFF B-cell activating factor, BAFFR B-cell activating factor receptor, IFNγ interferon γ, IFNγR interferon γ receptor, GC germinal center

Fig. 4

The immune pathogenesis of SLE and targets of SLE treatment (treatment targets are marked by red boxes). NETosis neutrophil extracellular trap formation, PMN polymorphonuclear neutrophils, DC dendritic cell, BDCA blood dendritic cell antigen, BCL B-cell lymphoma, IL interleukin, IFN interferon, TNF tumor necrosis factor, APRIL a proliferation-inducing ligand, BAFF B-cell activating factor, BCMA B-cell maturation antigen, TAIC transmembrane activator-1 and calcium modulator ligand interactor, ICOS inducible co-stimulator, ICOSL inducible co-stimulator ligand, HLA human leukocyte antigen, BCR B-cell receptor, BTK Bruton’s tyrosine kinase, MHC major histocompatibility complex, TCR T cell receptor, CXCR5 CXC chemokine receptor type 5