ALW peptide ameliorates lupus nephritis in MRL/lpr mice

Wang, Huixia; Lu, Mengji; Zhai, Siyue; Wu, Kunyi; Peng, Lifeng; Yang, Jie; Xia, Yumin

doi:10.1186/s13075-019-2038-0

Cited by 18 publications

(9 citation statements)

References 40 publications

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“…This confirms that lupus nephritis initiation is not due to a single factor [ 22 ]. Nonetheless, a large amount of research suggests that anti-dsDNA antibodies accelerate lupus nephritis processes, and lupus nephritis symptoms are improved by blocking anti-dsDNA antibodies [ 23 , 24 ]. We conclude that anti-dsDNA antibodies are involved in renal inflammation and fibrosis; however, further investigation is needed on the complex mechanism of the cytokine networks and signaling pathways.…”

Section: The Anti-dna Antibody-targeting Organsmentioning

confidence: 99%

“…This molecule can also prevent IgG isotypes or anti-dsDNA antibodies in SLE patients’ serum interacting with glomerulus and glomerular mesangial cells [ 24 ]. ALW peptides can inhibit glomerular deposition of antibodies, reduce serum anti-dsDNA antibody titers, improve renal pathological manifestations, or suppress proliferation, fibrosis, and inflammatory cell infiltration of renal tissue, providing a protective effect on lupus nephritis manifestation in MRL/lpr mice [ 23 ].…”

Section: Blockade Of Anti-dsdna Antibodiesmentioning

confidence: 99%

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The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies

Wang

Xiao

Xia

et al. 2021

Clinic Rev Allerg Immunol

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton’s tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.

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Section: The Anti-dna Antibody-targeting Organsmentioning

confidence: 99%

Section: Blockade Of Anti-dsdna Antibodiesmentioning

confidence: 99%

The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies

Wang

Xiao

Xia

et al. 2021

Clinic Rev Allerg Immunol

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“…Furthermore, deposition of immune reactants plays a pivotal role in the occurrence, development, and prognosis of LN as well (30). The cross-reaction between immunoglobulin (IgG/IgM) and renal antigens plays key regulatory roles in many biological processes, such as activation of complement cascades, regulation of gene expression and cell proliferation (31). And it induces phenotypic changes of glomerular resident cells, leading to kidney injury in LN (32).…”

Section: Discussionmentioning

confidence: 99%

1,25-dihydroxyvitamin D3 Ameliorates Lupus Nephritis Through Inhibiting NF-κB and MAPKs Signaling Pathways in MRL/lpr Mice

Zhao

et al. 2021

Preprint

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Background: Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). However, the etiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3（1,25-(OH)2-VitD3）is the active form of vitamin D, which has been known to have important functions in inflammation and immune diseases. In this study, we investigated Its protective effects and underlying mechanism in MRL/lpr mice, a well-studied animal model for lupus.Methods: At the age of 11 weeks, forty-eight MRL/lpr mice were randomly divided into two groups with 24 mice per group: the VitD3-treated group and control group. Mice in the VitD3-treated group received 4μg/kg 1,25-dihydroxyvitamin D3 in 1％ dimethyl sulfoxide (DMSO) intraperitoneal injection twice a week for 3 weeks (mice were executed at 0,2,4,6 weeks after treatment); mice in the control group treated with intraperitoneal injection of 1% DMSO for 3 weeks (mice were executed at 0,2,4,6 weeks after injections). The mice were sacrificed and the serum and kidney samples were collected respectively at planned intervals. Then the skin lesions, histological changes, inflammatory factors (TNF-α, IL-17) and immunological markers (A-ds DNA, C3, IgG, IgM) with time were analyzed between the groups. Furthermore, the NF-κB and MAPKs signaling pathways were also detected to explicate the underlying mechanism. Results: Compared to the control group, mice in the VitD3-treated group showed less skin lesions, less kidney injury, lower serum anti-ds DNA antibody, lower inflammatory cytokines TNF-α, IL-17 and higher serum complement C3; they also had less deposition of IgG, IgM and C3 within glomeruli. Moreover, the expressions of NF-κB and MAPKs signaling pathways were decreased, while those levels were increased with time.Conclusion: This study shows that 1,25-dihydroxyvitamin D3 exerts a protective effect against lupus nephritis via regulating the NF-κB and MAPKs signaling pathways, which will be developed as a potential agent for the treatment of Lupus nephritis. And the relationship between lupus activity and NF-kB and MAPKs signaling pathways with time was revealed.

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“…Administration of nucleosomal peptides to SNF1 mice delayed the onset of nephritis and improved survival (140); in the mechanistic analysis, an increment of regulatory T cells was shown, and a direct effect on B cells was not investigated. Finally, peptides that bind anti-DNA antibodies can prevent their pathogenicity in vivo (141,142).…”

Section: B Cell-based Therapeutics: Approaches and Experience With Mouse Modelsmentioning

confidence: 99%