Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease

Sikder, Suchandan; Williams, Natasha L.; Sorenson, Alanna E.; Alim, Abdul; Vidgen, Miranda E.; Moreland, Nicole J.; Rush, Catherine M.; Simpson, Robert S.; Govan, Brenda; Norton, Robert; Cunningham, Madeleine W.; McMillan, David; Sriprakash, Kadaba S.; Ketheesan, Natkunam

doi:10.1093/infdis/jix637

Cited by 35 publications

(75 citation statements)

References 45 publications

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“…Autoimmune disorders, induced by some other members of Streptococcus except S. anginosus , have also been reported. For example, group G Streptococcu s induced an autoimmune carditis mediated by IL-17A and interferon gamma in the Lewis rat model of rheumatic heart disease ( Sikder et al, 2018 ). A small fraction of children with S. pyogenes infections was reported to develop Sydenham’s chorea or pediatric autoimmune neuropsychiatric disorders ( Cutforth et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia

Zhang

You

et al. 2020

Front. Microbiol.

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Gut microbiota has been implicated in the pathogenesis of many autoimmune diseases. This is still an area of active research given that the role of gut microbiota on the primary immune thrombocytopenia (ITP) remains unclear. In this study, fecal samples of 30 untreated adult primary ITP patients and 29 healthy controls (HCs) were used to investigate the gut microbial community and metabolite profiles. Our results show that fecal bacteria such as Blautia , Streptococcus , and Lactobacillus are enriched, whereas bacteria such as Bacteroides are depleted in ITP patients. Notably, fecal metabolites such as fatty acyls and glycerophospholipids are enriched and strongly correlate with discrepant gut microbiota. Furthermore, combinations of Weissella and Streptococcus anginosus , or Cer (t18:0/16:0), Cer (d18:1/17:0), and 13-hydroxyoctadecanoic acid could provide good diagnostic markers for ITP. Moreover, a strong negative correlation was found between platelet count and altered gut microbiota such as S. anginosus and gut metabolites such as Cer (t18:0/16:0) in ITP. In conclusion, dysbiosis of both gut microbiota and metabolome develops in ITP patients compared to HCs. Several ITP-altered gut bacteria and metabolites can be diagnostic biomarkers for ITP, and are highly correlated with platelet count, suggesting that they may also play a role in ITP pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia

Zhang

You

et al. 2020

Front. Microbiol.

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“…Table 2 summarizes the host tissue protein antigens targeted by anti-streptococcal antibodies in disease and following immunization with group A streptococcal components. Table 3 summarizes the group A streptococcal cross-reactive antigens, of which the group A carbohydrate (6) and the M proteins (8, 97–101) are the most well investigated.…”

Section: Monoclonal Antibodies Identify Streptococcal Cross-reactive mentioning

confidence: 99%

Molecular Mimicry, Autoimmunity, and Infection: The Cross-Reactive Antigens of Group A Streptococci and their Sequelae

Cunningham

2019

Microbiol Spectr

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The group A streptococcus is associated with a group of diseases affecting the heart, brain, and joints and are collectively referred to as acute rheumatic fever. The streptococcal immune mediated sequelae, including acute rheumatic fever, are due to antibody and cellular immune responses that target antigens in the heart and brain as well as the group A streptococcal cross-reactive antigens as reviewed below in this chapter. The pathogenesis of acute rheumatic fever, rheumatic heart disease, Sydenham chorea, and other autoimmune sequelae is related to autoantibodies that are characteristic of autoimmune diseases and result from the immune responses against the group A streptococcal infection by the host. The sharing of host and streptococcal epitopes leads to molecular mimicry between the streptococcal and host antigens that are recognized by the autoantibodies during the host response. The chapter elaborates on the discoveries that led to a better understanding of the pathogenesis of disease and provides an overview of the history and the most current thought about the immune responses against the host and streptococcal cross-reactive antigens in group A streptococcal sequelae.

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“…In this experiment, we performed echocardiography before and after the administration of the vaccine. The use of echocardiography was recently used in a rat model for RHD 45 . The authors were able to observe valvar fibrosis with nodules in rats treated with whole-killed group G streptococci similar to GAS M5 (a rheumatogenic strain).…”

Section: Discussionmentioning

confidence: 99%

Group A Streptococcus Adsorbed Vaccine: Repeated Intramuscular Dose Toxicity Test in Minipigs

Postol

Sá-Rocha

Sampaio

et al. 2019

Sci Rep

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Streptococcus pyogenes infection continues to be a worldwide public health problem causing various diseases in humans and plays an important role in the pathogenesis of rheumatic fever and rheumatic heart disease. We developed a vaccine candidate to prevent S. pyogenes infections, identified as StreptInCor, that presented promising results in mouse models. A certified and independent laboratory conducted two repeated intramuscular dose toxicity tests (28 days, four weekly injections). The first test, composed of four experimental groups treated with 0 (vehicle), 50, 100 or 200 µg/500 µL StreptInCor, did not show significant alterations in clinical, hematological, biochemical or anatomopathological parameters related to the administration of StreptInCor. In addition to the parameters mentioned above, we evaluated the cardiac function and valves of animals by echocardiography before and after administration of 200 µg/500 µL StreptInCor versus placebo. We did not observe any changes related to StreptInCor administration, including changes in cardiac function and valves in animals, after receiving the highest dose of this vaccine candidate. The results obtained in the two repeated intramuscular dose toxicity tests showed that this vaccine formulation did not induce harmful effects to the tissues and organs studied, indicating that the candidate vaccine is well tolerated in minipigs.

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Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease

Cited by 35 publications

References 45 publications

Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia

Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia

Molecular Mimicry, Autoimmunity, and Infection: The Cross-Reactive Antigens of Group A Streptococci and their Sequelae

Group A Streptococcus Adsorbed Vaccine: Repeated Intramuscular Dose Toxicity Test in Minipigs

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