Decreased DNA hydroxymethylation and increased DNA demethylation are associated with high antioxidant response in systemic lupus erythematosus patients

The aberrant activity of CD4+T cells in patients with systemic lupus erythematosus (SLE) is associated with DNA hypomethylation of the regulatory regions in CD11a and CD70 genes. Our previous studies demonstrated that Gadd45a contributes to the development of SLE by promoting DNA demethylation in CD4+T cells. In this study, we identified proteins that bind to Gadd45a in CD4+T cells during SLE flare by using the method of co-immunoprecipitation and mass spectrometry, High mobility group box protein 1 (HMGB1) is one of identified proteins. Furthermore, gene and protein expression of HMGB1 was significantly increased in SLE CD4+T cells compared to controls, and HMGB1 mRNA was correlated with CD11a and CD70 mRNA. A significant, positive correlation was found between HMGB1 mRNA and SLEDAI for SLE patients. Our data demonstrate that HMGB1 binds to Gadd45a and may be involved in DNA demethylation in CD4+T cells during lupus flare.

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CircIBTK inhibits DNA demethylation and activation of AKT signaling pathway via miR-29b in peripheral blood mononuclear cells in systemic lupus erythematosus

Arthritis Research & Therapy ◽

10.1186/s13075-018-1618-8 ◽

2018 ◽

Vol 20 (1) ◽

Cited By ~ 25

Author(s):

Xin Wang ◽

Chengzhong Zhang ◽

Zhouwei Wu ◽

Yue Chen ◽

Weimin Shi

Keyword(s):

Systemic Lupus Erythematosus ◽

Peripheral Blood Mononuclear Cells ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Akt Signaling ◽

Dna Demethylation ◽

Akt Signaling Pathway ◽

Systemic Lupus ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Organized Intraglomerular Deposits in NZB Mouse Disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066772 ◽

1971 ◽

Vol 29 ◽

pp. 544-545

Author(s):

Francis R. Comerford ◽

Alan S. Cohen

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antinuclear Antibodies ◽

Human Systemic Lupus Erythematosus ◽

Systemic Lupus ◽

Glomerular Lesion ◽

Ultrastructural Studies ◽

Dense Deposits ◽

Experimental Nephritis ◽

Glomerular Lesions

Mice of the inbred NZB strain develop a spontaneous disease characterized by autoimmune hemolytic anemia, positive lupus erythematosus cell tests and antinuclear antibodies and nephritis. This disease is analogous to human systemic lupus erythematosus. In ultrastructural studies of the glomerular lesion in NZB mice, intraglomerular dense deposits in mesangial, subepithelial and subendothelial locations were described. In common with the findings in many examples of human and experimental nephritis, including many cases of human lupus nephritis, these deposits were amorphous or slightly granular in appearance with no definable substructure.We have recently observed structured deposits in the glomeruli of NZB mice. They were uncommon and were found in older animals with severe glomerular lesions by morphologic criteria. They were seen most commonly as extracellular elements in subendothelial and mesangial regions. The deposits ranged up to 3 microns in greatest dimension and were often adjacent to deposits of lipid-like round particles of 30 to 250 millimicrons in diameter and with amorphous dense deposits.

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