Jim Hoffman: Targeting Extracorporeal Removal of Extracellular Chromatin to Mitigate Lupus Pathogenesis
Jim Hoffman, Former Technical Advisor at Cygnus Technologies, LLC, posted on LinkedIn about a recent article by Neelakshi R. Jog et al, published in Wiley Online Library:
“Older, but highly relevant, translational evidence is provided by Jog et al, suggesting we should be targeting extracorporeal removal of extracellular chromatin as a therapy to help mitigate the pathogenesis of lupus-like diseases, where nuclear chromatin and NETs are known to be chronically elevated and apoptotic cell body clearance is insufficient, and efferocytosis is impaired.
Particularly, when normal basal levels of nuclear chromatin/NETs remain persistently elevated extracellularly in the blood, other body fluids, and tissues in response to infectious and non-infectious disease triggers.
Caspase-activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens.
‘In accordance with findings in the CAD-mutant Sle1 and Sle123 mice, CAD-deficient 3H9 mice spontaneously generated anti-DNA antibodies. Finally, we showed that autoantibodies with specificities toward histone-DNA complexes bind more to CAD-deficient apoptotic cells than to CAD-sufficient apoptotic cells.’
‘These results strongly suggest that in mice genetically predisposed to autoimmunity, the absence of chromatin fragmentation and the resulting abnormal display of apoptotic AutoAgs, result in failure to achieve anergy and instead promote B cell autoreactivity.'”
Title: Caspase-activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens
Authors: Neelakshi R. Jog, Lorenza Frisoni, Qin Shi, Marc Monestier, Sairy Hernandez, Joe Craft, Eline T. Luning Prak, Roberto Caricchio
Read the Full Article on Wiley Online Library.
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