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Post-Streptococcal Autoimmune Sequelae: Rheumatic Fever and Beyond.

Authors

Cunningham MW4.

Editors

In: Ferretti JJ1, Stevens DL2, Fischetti VA3, editors.

Source

Streptococcus pyogenes : Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2016-.
2016 Feb 10.

Author information

1
University of Oklahoma Health Sciences Center, Oklahoma City, OK
2
VA Medical Center, Boise, ID
3
The Rockefeller University, New York, NY
4
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center, Oklahoma City, OK

Excerpt

Molecular mimicry between the group A streptococcus, heart, and brain is supported by evidence from studies of human mAbs, human T cell clones, and serum IgG antibodies derived from streptococcal sequelae and rheumatic fever (Galvin, Hemric, Ward, & Cunningham, 2000; Kirvan, Swedo, Heuser, & Cunningham, 2003). Human mAbs derived from rheumatic carditis and Sydenham chorea have supported the hypothesis that antibodies against the group A streptococcal carbohydrate epitope GlcNAc recognize cross-reactive structures in the heart and brain, which can lead to rheumatic carditis/rheumatic heart disease and Sydenham chorea, respectively (Galvin, Hemric, Ward, & Cunningham, 2000; Kirvan, Swedo, Heuser, & Cunningham, 2003). The rheumatic valve has been linked to humoral immune responses that attack the endocardium and allow activated T cells cross-reactive with cardiac myosin and streptococcal M protein epitopes to enter through activated VCAM-1+ endothelium at the valve surface (Roberts, et al., 2001). Although a Th1 response was observed by Guilherme et al. in the valve (Guilherme, et al., 2004), Th17 cells have also been recognized to have the potential for importance in the pathogenesis of rheumatic heart disease, where the balance between Th17 and T regulatory lymphocyte subsets was altered in disease that favored the Th17 subset. (Bas, et al., 2014). As early as 1989, Bhatia et al. reported changes in the lymphocyte subsets (Bhatia, et al., 1989). Changes in the subsets may lead to a Th17 predominance in disease with excess antibody production, including the cross-reactive antibodies, as well as the formation of immune complexes. Th17 cells have been established in responses against group A streptococci (Dileepan, Linehan, Moon, Pepper, & Jenkins, 2011; Wang, et al., 2010) and extracellular pathogens. Antibody-mediated neuronal cell signaling may be an important mechanism of antibody pathogenesis in Sydenham chorea, as well as in diseases such as PANDAS and PANS. The emerging theme in mimicry suggests that cross-reactive autoantibodies target intracellular antigens, but to be pathogenic, antibodies must also target the surface antigens of neuronal cells or valve endothelial cells by targeting extracellular matrix proteins on the heart valve, such as laminin (Galvin, Hemric, Ward, & Cunningham, 2000), or binding to receptors such as the dopamine receptors which signal neurons (Cox, et al., 2013) or by other inflammatory effects caused by immune complexes of cross-reactive antibodies (Nelson, et al., 2015; Zhang, et al., 2002).

© The University of Oklahoma Health Sciences Center.

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