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Title:
Molecular and Immunological Basis of Tubulo-Interstitial Injury in Lupus Nephritis: a Comprehensive Review | Clinical Reviews in Allergy & Immunology
Description:
Lupus nephritis is an important cause of kidney failure in patients of Asian, African, or Hispanic descent. Its etiology and pathogenesis are multifactorial and remain to be elucidated. Accumulating evidence suggests that anti-double-stranded DNA (dsDNA) antibodies play a critical role in the pathogenesis, through its direct binding to cross-reactive antigens on resident renal cells or indirect binding through chromatin material to extracellular matrix components, resulting in complement activation, cell activation and proliferation, and induction of inflammatory and fibrotic processes. While tubulo-interstitial damage portends poor long-term renal prognosis, the mechanisms leading to tubulo-interstitial injury in lupus nephritis has received relatively less attention to date. Immune deposition along the tubular basement membrane is often observed in lupus nephritis and correlates with tubulo-interstitial infiltration of immune cells and interstitial fibrosis. Anti-dsDNA antibodies bind to resident renal cells, including proximal renal tubular epithelial cells, and contribute to renal inflammation and fibrosis. There is emerging evidence that epigenetic influence such as DNA methylation, histone modification, and microRNAs (miRs) also contribute to kidney fibrosis. Overexpression of miR-150 is observed in renal biopsies from patients with lupus nephritis and correlates with kidney fibrosis and chronicity score. Mycophenolate mofetil (MMF) is an established and effective standard-of-care therapy for patients with lupus nephritis. Accumulating data suggest that in addition to its immunosuppressive actions on lymphocyte proliferation, mycophenolic acid (MPA), the active metabolite of MMF, can exert a direct effect on nonimmune cells. Mediators of inflammation and fibrosis induced by anti-dsDNA antibodies in cultured proximal renal tubular epithelial cells are ameliorated by the addition of MPA, suggesting that in addition to its immunosuppressive actions, MPA may also have a beneficial effect in improving tubulo-interstitial inflammation and fibrosis through its direct action on proximal renal tubular epithelial cells.
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Keywords {🔍}

pubmed, google, scholar, article, cas, lupus, central, kidney, nephritis, renal, fibrosis, nephrol, systemic, antibodies, erythematosus, cells, chan, human, int, cell, fibronectin, tubular, epithelial, yung, dna, antidna, soc, immunol, clin, glomerular, disease, expression, tubulointerstitial, injury, patients, proximal, protein, mice, mycophenolate, acid, pathol, med, wang, mofetil, autoantibodies, zhang, molecular, role, mechanisms, basement,

Topics {✒️}

serum mir-130b-3p level anti-double-stranded dna antibodies platelet-derived growth factor month download article/chapter tumor necrosis factor-alpha anti-dsdna antibodies bind tak mao chan transforming growth factor-beta improving tubulo-interstitial inflammation tumour necrosis factor-alpha anti-double-stranded dna developing anti-dna antibodies anti-dna idiotypes deposited anti-dsdna autoantibody production nephritogenic anti-dna antibodies anti-dna antibody induction human anti-dna antibodies pathogenic anti-dna antibodies murine anti-dna antibodies anti-nucleosome antibodies complexed cytosine-phosphate-guanine dnmt1 anti-ds dna antibodies human anti-fibronectin antibodies article clinical reviews long-term study anti-dsdna antibodies tubular basement membrane van vliet ai cross-reactive renal target central target structures human renal proximal tubular epithelial cells end-stage renal disease renal tubular cells full article pdf anti-dna antibodies tubulo-interstitial infiltration glomerular basement membrane mrl-lpr/lpr mouse hong kong chinese nzb/nzw f1 mice tubulo-interstitial injury double stranded dna renal interstitial fibrosis distal tubular cells anti-nucleosome antibodies extracellular matrix components study lupus glomerulonephritis mycophenolic acid antagonizes mrl-fas lpr mice

Questions {❓}

Isenberg DA, Manson JJ, Ehrenstein MR, Rahman A (2007) Fifty years of anti-ds DNA antibodies: are we approaching journey’s end?
Jeffries MA, Sawalha AH (2015) Autoimmune disease in the epigenetic era: how has epigenetics changed our understanding of disease and how can we expect the field to evolve?
Rekvig OP, Nossent JC (2003) Anti-double-stranded DNA antibodies, nucleosomes, and systemic lupus erythematosus: a time for new paradigms?
What is damaging the kidney in lupus nephritis?

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