title: Post-infectious group A streptococcal autoimmune syndromes and the heart.
abstract: There is a pressing need to reduce the high global disease burden of rheumatic heart disease (RHD) and its harbinger, acute rheumatic fever (ARF). ARF is a classical example of an autoimmune syndrome and is of particular immunological interest because it follows a known antecedent infection with group A streptococcus (GAS). However, the poorly understood immunopathology of these post-infectious diseases means that, compared to much progress in other immune-mediated diseases, we still lack useful biomarkers, new therapies or an effective vaccine in ARF and RHD. Here, we summarise recent literature on the complex interaction between GAS and the human host that culminates in ARF and the subsequent development of RHD. We contrast ARF with other post-infectious streptococcal immune syndromes - post-streptococcal glomerulonephritis (PSGN) and the still controversial paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), in order to highlight the potential significance of variations in the host immune response to GAS. We discuss a model for the pathogenesis of ARF and RHD in terms of current immunological concepts and the potential for application of in depth "omics" technologies to these ancient scourges.
authors.affiliation: Inflammation Division, Water and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: martin@wehi.edu.au.
authors.forename: William John
authors.initials: WJ
authors.lastname: Martin
authors.affiliation: Centre for International Child Health, Department of Pediatrics, University of Melbourne and Murdoch Childrens Research Institute, Parkville, VIC 3052, Australia; Group A Streptococcus Laboratory, Murdoch Childrens Research Institute, Parkville, VIC 3052, Australia.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Steer
authors.affiliation: Centre for International Child Health, Department of Pediatrics, University of Melbourne and Murdoch Childrens Research Institute, Parkville, VIC 3052, Australia; Group A Streptococcus Laboratory, Murdoch Childrens Research Institute, Parkville, VIC 3052, Australia.
authors.forename: Pierre Robert
authors.initials: PR
authors.lastname: Smeesters
authors.affiliation: Inflammation Division, Water and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Keeble
authors.affiliation: Medical Systems Biology, Department of Pathology and Department of Microbiology and Immunology, University of Melbourne, VIC 3010, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.affiliation: Telethon Kids Institute, University of Western Australia, WA, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carapetis
authors.affiliation: Inflammation Division, Water and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Rheumatology Unit, Royal Melbourne Hospital, Parkville, VIC 3052, Australia. Electronic address: wicks@wehi.edu.au.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Wicks
mesh_terms: D000818:Animals; D003937:Diagnosis, Differential; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000209:etiology*; D006801:Humans; D012213:Rheumatic Fever / Q000209:etiology*; D012214:Rheumatic Heart Disease / Q000209:etiology*; D013290:Streptococcal Infections / Q000150:complications*
keywords: Acute rheumatic fever; Autoimmunity; Glomerulonephritis; Group A streptococcus; PANDAS; Rheumatic heart disease