. 2017 May 25;8(5):e2812. doi: 10.1038/cddis.2017.52

Table 3. Therapeutic approaches and potential anti-histone therapies.

Blocking release	Neutralisation	Blocking signalling
PAD4i⁶⁰	Anti-H mAb^{2, 16, 19, 35, 36, 53, 57, 58, 59}	TLR blocking mAb
Blocks NETosis	Neutralises histone in circulation	PreventsTLR2/4/9 signal transduction
Inhibits citrullination of H3	DNase1⁵⁵	Reduces cytokine release
DNase1⁵⁷	Degrades NET linker-DNA	Significant immunosuppressive side effects likely
Disperses NET-derived histone within circulation	Disperses histone	CRP⁷³
Prevents NET-mediated NETosis	aPC³⁵	Endogenous anionic acute phase protein
	Serum protease	Prevents cationic histone from binding to phosphodiester bonds on phospholipids
	Degrades eHistone
	PSA³⁵
	Endogenous Anionic protein
	Ionic interaction with H

Abbreviations: aPC, activated Protein C; BWA3, H4 histone neutralising antibody; CRP, C-reactive protein; H, histone; NET, neutrophil extracellular trap; NETosis, NET release; PAD4i, protein arginine deiminase 4; PSA, polysialic acid; TLR, Toll-like receptor