Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus

• DOI: 10.1172/jci.insight.136678
• Publication Date: 2022-05-24T16:00:44Z
• Authors: David M. Patrick; Néstor de la Visi...; Jaya Krishnan; Wei Chen; Michelle J. Ormseth; C. Michael Stein; Sean S. Davies; Venkataraman Amar...; Leslie J. Crofford; Jonathan M. Williams; Shilin Zhao; Charles D. Smart; Sergey Dikalov; Anna Dikalova; Liang Xiao; Justin P. Van Beu...; Mingfang Ao; Agnes B. Fogo; Annet Kirabo; David G. Harrison
• Keywords: Inflammation; Complement C1q; R; Autoimmunity; Lipids; 3. Good health; Mice; Antibodies, Antinuclear; Hypertension; Medicine; Animals; Lupus Erythematosus, Systemic; Erratum; Research Article

We describe a mechanism responsible for systemic lupus erythematosus (SLE). In humans with SLE and in 2 murine models, there was marked enrichment of isolevuglandin-adducted proteins (isoLG adducts) monocytes dendritic cells. found that antibodies formed against isoLG adducts both SLE-prone mice SLE. addition, ligation the transcription factor PU.1 at critical DNA binding site markedly reduced all C1q subunits. Treatment specific scavenger 2-hydroxybenzylamine (2-HOBA) ameliorated parameters autoimmunity, including plasma cell expansion, circulating IgG levels, anti-dsDNA antibody titers. 2-HOBA also lowered blood pressure, attenuated renal injury, inflammatory gene expression uniquely C1q-expressing Thus, play an essential role genesis maintenance autoimmunity hypertension