Cell- and nuclear-penetrating anti-dsDNA autoantibodies have multiple arginines in CDR3 of VH and increase cellular level of pERK and Bcl-2 in mesangial cells

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

“…Anti-dsDNA monoclonal antibodies 2C10 and G5-8 IgGs were obtained from the mouse model MRL-lpr/lpr (Im et al 2015). 2C10 VH domain was produced from 2C10 IgG by recombinant technology (Im et al 2017).…”

“…Anti-double stranded DNA (dsDNA) autoantibodies (autoAbs) can be characteristically found in patients with SLE and LN. There is accumulating evidence for the pathogenic role of antidsDNA autoAbs in induction and progress of the diseases (Jang et al 1996;Putterman 2004;Isenberg et al 2007;Im et al 2015). It has been reported by different research groups including ourselves that some autoAbs have cell-penetrating properties, and this subset of Abs could be involved in pathogenesis (Alarcon-Segovia et al 1978;Lee et al 2007;Jang et al 2009;Im et al 2015).…”

“…Recently, it has been reported that cellpenetrating anti-dsDNA autoAbs have multiple arginines in the complementarity determining region 3 of variable heavy domain (CDR3-VH) and one of the Abs, 2C10 IgG and its recombinant VH, penetrate cells (Im et al 2015(Im et al , 2017 and increase the levels of pERK1/2 and Bcl-2 in renal mesangial (MES) cells, the main target in LN (Im et al 2015). 2C10 IgG has been produced from the SLE mouse model MRL-lpr/lpr (Stollar et al 1986;Kubota et al 1996;Im et al 2015). The recombinant 2C10 VH single domain has been produced by engineering the structure of 2C10 IgG (Im et al 2015(Im et al , 2017.…”

“…2C10 IgG has been produced from the SLE mouse model MRL-lpr/lpr (Stollar et al 1986;Kubota et al 1996;Im et al 2015). The recombinant 2C10 VH single domain has been produced by engineering the structure of 2C10 IgG (Im et al 2015(Im et al , 2017. The penetrating autoAbs can amplify disease severity by affecting the target cells in various ways (Kubota et al 1996;Sun et al 2000;Yu et al 2001;Lee et al 2007;Jang et al 2009;Im et al 2015).…”

“…The recombinant 2C10 VH single domain has been produced by engineering the structure of 2C10 IgG (Im et al 2015(Im et al , 2017. The penetrating autoAbs can amplify disease severity by affecting the target cells in various ways (Kubota et al 1996;Sun et al 2000;Yu et al 2001;Lee et al 2007;Jang et al 2009;Im et al 2015). Cytokines released by MES cells could lead to stimulation of other pro-inflammatory cytokines and inflammation of renal tissues, resulting in kidney damage (Graninger et al 2000;Feng et al 2012).…”