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Review
. 2023 Aug;43(8):1381-1393.
doi: 10.1007/s00296-023-05346-x. Epub 2023 May 24.

Systemic lupus erythematosus: latest insight into etiopathogenesis

Akhil Akhil  1 , Rohit Bansal  1 , Kumari Anupam  2 , Ankit Tandon  3 , Archana Bhatnagar  4
Affiliations
Review

Systemic lupus erythematosus: latest insight into etiopathogenesis

Akhil Akhil et al. Rheumatol Int. 2023 Aug.

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options.

Keywords: Environmental factors; Epigenetics; Etiology; Immunobiology; Lupus; Multifactorial interactions.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
The complex interactions between the various susceptible factors implicated in lupus etiology. Implications of genetics known to directly regulate the disease manifestations or indirectly through epigenetic modifications induced by environmental factors. These indirect modifications can also regulate the immunobiology and mitochondrial health which combines to affect the immunometabolism, an important aspect in lupus pathology. Diet is equally important as it can regulate the disease severity and hence assist in disease management
Fig. 2
Fig. 2
Immunobiology of systemic lupus erythematosus. Interaction between dysregulated innate and adaptive immune system leads to production of inflammatory cytokines and autoantibody. Over-activation of innate system further interacts with the adaptive immune system leads to over-activation of various immune cells. Self-antigen presentation by dendritic cells leads to the activation of T cells that further activates the autoreactive B cells and secretes the autoantibodies. FcR Immunoglobulin Fc receptors, TLR Toll-like receptor, BAFF B cell activating factors, IL Interleukin
Fig. 3
Fig. 3
Recently elucidated mechanisms and their interactions involved in systemic lupus erythematosus (SLE) modification. Regulation of innate response and enhanced pro-inflammatory cytokines secretion through polymorphism have been recently identified in SLE. Role of mitochondrial dysfunction and associated oxidative stress in metabolic alterations and their impact on immune cell activity and differentiation have been majorly focused in recent studies on SLE. Novel signaling mechanisms have also been elaborated related to metabolic fitness of T cell and their importance in SLE immunobiology. Implications of inflammatory cytokines rich microenvironment on immune cell differentiation specifically, on T cells has been recently focused in SLE related studies. SNP Single nucleotide polymorphism, TLR toll- like receptor, HIF-1α Hypoxia inducing factor 1α, PER2 Period circadian protein homolog 2, DNMT3B DNA-methyltransferase 3 beta, VDAC voltage- dependent anion channel, EZH2 Enhancer of zeste homolog 2, PKC protein kinase C, STAT6 signal transducer and activator of transcription 6, GATA3 GATA binding protein 3, pDC plasmacytoid dendritic cells, ITAM Immunoreceptor tyrosine-based activation motif, ZAP-70 Zeta chain associated protein kinase 70 mTORC1 mammalian target of rapamycin complex 1, IRAK interleukin-1 receptor-associated kinases, IFNα interferon α, Ras-MPK Ras-mitogen-activated protein kinase, Cxcl10 C-X-C motif chemokine ligand 10, ISGs interferon stimulated genes, CD3 cluster of differentiation 3
Fig. 4
Fig. 4
Epigenetics implications modifies the various mechanisms involved in lupus pathology. Oxidative stress and diet have been recently shown as the important triggers of the epigenetic events demonstrates the importance of environmental factors in disease etiology. Methylation patterns have been found potentially involved in modulation of immunobiology via regulating the T reg and B cell activity. Hypermethylation of the anti-inflammatory sites and hypomethylation of pro-inflammatory genes have been demonstrated in recent studies. Epigenetic events can potentially modulate the lupus outcomes and can be utilized for diagnosis as biomarkers. SNP single-nucleotide polymorphism, BAFF B-cell activating factor, IFI 44L Interferon-inducible 44 like, PBMC Peripheral blood mononuclear cells, FOXP3 forkhead box P3, BDH2 3-hydroxybutyrate dehydrogenase 2, TET ten–eleven translocation, ROS reactive oxygen species
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References

    1. Alaanzy MT, Alsaffar JM, Bari AA. Evaluate the correlation between antioxidant capacity and interferon Γ level with the disease activity of Sle patients in Iraqi Woman. Indian J Public Health Res Dev. 2020;11(1):1278–1282. doi: 10.37506/v11/i1/2020/ijphrd/194018. - DOI
    1. Terahara N. Flavonoids in foods: a review. Nat Prod Commun. 2015;10(3):19345781501000334. - PubMed
    1. Mok C, Lau C. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56(7):481–490. doi: 10.1136/jcp.56.7.481. - DOI - PMC - PubMed
    1. Adams DE, Shao W-H. Epigenetic alterations in immune cells of systemic Lupus erythematosus and therapeutic implications. Cells. 2022;11(3):506. doi: 10.3390/cells11030506. - DOI - PMC - PubMed
    1. Katsuyama T, Tsokos GC, Moulton VR. Aberrant T cell signaling and subsets in systemic lupus erythematosus. Front Immunol. 2018;9:1088. doi: 10.3389/fimmu.2018.01088. - DOI - PMC - PubMed