Pathogenic effect of a cell-penetrating anti-dsDNA autoantibody through p38 signaling pathway and pro-inflammatory cytokine stimulation in mesangial cells

Pravinsagar, Pavithra; Im, Sun-Woo; Jang, Young-Ju

doi:10.1080/19768354.2017.1401557

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…Data from these studies demonstrated the deposition of these antibodies in various kidney structures, including tubules, glomeruli, mesangium, basement membrane, subendothelial, and surrounding spaces. In this regard, data from the literature indicated that the high titer of anti-dsDNA could develop LN and positively correlated with the activity of nephritis [12,13]. Contrary to the abovementioned ndings, a few numbers of the patients with SLE and also LN, ranging from 5-30%, has no detectable circulating anti-dsDNA antibodies [6,14].…”

Section: Introductionmentioning

confidence: 89%

The Concurrent Anti-C1q and Anti-dsDNA but not Anti-C3b Antibodies as Potent Biomarkers for Lupus Nephritis prediction

Kianmehr¹,

Khoshmirsafa²,

Shekarabi³

et al. 2020

Preprint

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Background: Lupus Nephritis (LN) in patients with Systemic Lupus Erythematosus (SLE) is one of the most serious and prevalent manifestations. The procedure of renal biopsy is harmful and accompanied by potential hazards. Therefore, introducing reliable biomarkers to predict LN is exceedingly worthwhile. In the current study, we compared the diagnostic values of circulating autoantibodies against dsDNA, C1q, C3b, SSA, SSB, and Sm alone or in combination to predict LN.Methods: This study evaluated abovementioned autoantibodies in 40 healthy controls (HCs) and 95 SLE patients with different kidney involvements, including absent (n = 40), inactive (n = 20), and active (n= 35) LN using EIA method.Result: The frequency and odds ratio of anti-dsDNA (71.4%, OR=4.2), anti-C1q (62.9%, OR= 5.1), and the simultaneous existence of anti-C1q and anti-dsDNA (51.4%, OR=6) antibodies were significantly higher in the active LN group compared with both inactive and absent LN groups. Moreover, the levels of anti-C1q and anti-dsDNA antibodies positively correlated with disease activity in patients with SLE. The prevalence of these autoantibodies was associated with the severity of LN biopsies. Conclusion: These data suggest that anti-C1q and anti-dsDNA antibodies and also the simultaneous presence of them may be valuable diagnostic biomarkers for LN prediction in patients with SLE.

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Section: Introductionmentioning

confidence: 89%

The Concurrent Anti-C1q and Anti-dsDNA but not Anti-C3b Antibodies as Potent Biomarkers for Lupus Nephritis prediction

Kianmehr¹,

Khoshmirsafa²,

Shekarabi³

et al. 2020

Preprint

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“…Anti-dsDNA Abs are able to penetrate several different cell types, including cancer cell lines and normal cells, and trigger the activation of pro-inflammatory cytokine production and signaling molecules. 6,9–11 Here, we demonstrate that the LN autoantigen TNP1 could amplify the inflammatory reaction in macrophages. TNP1 enhanced the levels of IFN-α and IL-6 triggered by anti-dsDNA auto-mAbs, G2-6 and G5-8, in a macrophage cell line, suggesting a possible involvement of the anti-dsDNA-TNP1 complex in the provocation of the inflammatory reaction.…”

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

“…6,8 Anti-dsDNA mAbs with cell-penetrating activities are able to induce NF-κB activation; stimulate the secretion of pro-inflammatory cytokines, interleukin-6 (IL-6), interferon-α (IFN-α), tumor necrosis factor-α, IL-1β, IL-10, IL-33, and monocyte chemoattractant protein-1; and induce the activation of p38, RSK-1, Bcl-2, and ATF-2 molecules in mouse macrophages, mesangial cells, and human peripheral blood mononuclear cells. [9][10][11] Serum levels of IL-6 and IFN-α have been implicated as important factors in the pathological process of LN/SLE. IL-6 and IFN-α correlate strongly with disease severity in patients as well as in murine models.…”

Section: Introductionmentioning

confidence: 99%

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Autoantigen spermatid nuclear transition protein 1 enhances pro-inflammatory cytokine production stimulated by anti-DNA autoantibodies in macrophages

2022

Self Cite

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Introduction Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE), is associated with high fatality rate in patients. The pathogenesis of lupus nephritis is complex and has not been fully elucidated. Kidney inflammation, renal cell damage, and accumulation of immune complexes in the glomerular basement membrane often occur in patients with lupus nephritis. Spermatid nuclear transition protein 1 (TNP1) might be a potentially interesting autoantigen in exploring the pathogenesis and therapy of lupus nephritis. Objective This study aimed to explore the effect of TNP1 and its complexes with anti-double-stranded DNA antibodies on the levels of interleukin-6 (IL-6) and interferon-α (IFN-α) in vitro. Methods We studied the effect of the synthetic peptide of the autoantigen on the pathogenic characteristics of the G2-6 and G5-8 antibodies in mouse macrophages, using enzyme-linked immunosorbent assay, quantitative RT-PCR, western blotting, and flow cytometry. Results The antibodies exhibited cross-reactivity to spermatid TNP1 in direct-binding and competitive enzyme-linked immunosorbent assay. Results of quantitative RT-PCR and western blotting revealed that the antibodies alone enhanced the levels of IL-6 and IFN-α transcripts and proteins, respectively. Flow cytometry revealed that treatment with the autoantigen enhanced the cell-penetrating activities of G2-6 and G5-8 and remarkably increased the cytokine levels. Conclusion TNP1 enhanced the cell-penetrating activities of anti-dsDNA auto-Abs, G2-6 and G5-8, and remarkably increased the levels of IL-6 and IFN-α in macrophages, suggesting that TNP1 and cell-penetrating pathogenic anti-dsDNA auto-Abs is potential targets for future therapeutic approaches to treat LN/SLE.

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Nanobodies as molecular imaging probes

Barakat

Berksoz

Zahedimaram

et al. 2022

Free Radical Biology and Medicine

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Pathogenic effect of a cell-penetrating anti-dsDNA autoantibody through p38 signaling pathway and pro-inflammatory cytokine stimulation in mesangial cells

Cited by 5 publications

References 42 publications

The Concurrent Anti-C1q and Anti-dsDNA but not Anti-C3b Antibodies as Potent Biomarkers for Lupus Nephritis prediction

The Concurrent Anti-C1q and Anti-dsDNA but not Anti-C3b Antibodies as Potent Biomarkers for Lupus Nephritis prediction

Autoantigen spermatid nuclear transition protein 1 enhances pro-inflammatory cytokine production stimulated by anti-DNA autoantibodies in macrophages

Nanobodies as molecular imaging probes

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