@article {25105,
	title = {A novel aspect may explain the mechanisms of pathogenicity of rheumatic fever, a multifactorial, autoimmune, infectious and inflammatory disorder which \&ldquo;licks the joints and bites the heart\&rdquo;: A working hypothesis},
	journal = {Medical Hypotheses},
	volume = {144},
	year = {2020},
	abstract = {A novel hypothesis is presented to explain the pathogenesis of the multifactorial autoimmune disorder rheumatic fever (RF). It involves a synergistic interaction among streptococcal toxins, their cell wall components, M protein, immune complexes, complement components, cationic histones. These agents can act with cationic histones released by neutrophils during NETosis and bacteriolysis and can function as opsonic agents possessing properties similar to antibodies. Cationic histones can interact by strong electrostatic forces with negatively- charged domains on immune complexes and complement components. This allows their deposition and endocytosis in the myocardium, the heart valves, and in the joints. However, the main cause of cell and tissue damage observed in RF is due to a synergism among the plethora of pro-inflammatory substances released by activated neutrophils and macrophages. Cell damage may be mitigated to some extent by anionic heparins, heparinoids, and by anti-inflammatory drugs such as corticosteroids which counteract neutrophils and macrophage chemotaxis induced by cytokines.},
	url = {https://www.sciencedirect.com/science/article/pii/S030698772031402X},
	author = {Issac Ginsburg and Mark Feldman}
}
