How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease

Faé, Kellen C.; Oshiro, Sandra E.; Toubert, Antoine; Charron, Dominique; Kalil, Jorge; Guilherme, Luiza

doi:10.1016/j.jaut.2005.01.007

Cited by 46 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mononuclear cells obtained from valve lesions of patients with rheumatic heart disease secreted tumor necrosis factor (TNF) and interferon gamma (IFNγ), suggesting that the CD4+ T cells were of the Th1 phenotype. Interleukin-10 (IL-10), a negative regulator of Th1 cells, was also secreted by the valve-infiltrating lymphocytes [30, 31]. …”

Section: Animal Models Of Autoimmune Endocarditismentioning

confidence: 99%

Autoimmune Valvular Carditis

Breed

Binstadt

2014

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

Autoimmune carditis is associated with many human rheumatic conditions, including rheumatic fever, systemic lupus erythematosous, and rheumatoid arthritis. The immune mechanisms that mediate the cardiovascular pathology connected to these diseases are poorly defined. Several animal models are used to recapitulate human pathophysiology in order to better characterize the immunopathogenic mechanisms driving autoimmune endocardial inflammation. These animal models point toward common mechanisms mediating autoimmune endocarditis; in particular, CD4+ T cells and pro-inflammatory macrophages play critical roles in directing the disease process. The goals of this review are to discuss the prevailing animal models of autoimmune endocarditis and their underlying immunologic mechanisms, and to provide insight regarding potential therapeutic targets in humans.

show abstract

Section: Animal Models Of Autoimmune Endocarditismentioning

confidence: 99%

Autoimmune Valvular Carditis

Breed

Binstadt

2014

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

show abstract

“…Certain unique phenotypic features of the pathogen pose particular challenges to vaccination(Pandey et al, 2012), including the invariant GAS capsule composed of hyaluronic acid (Kendall et al, 1937), an immunologically inert carbohydrate ubiquitous in human connective tissues. In addition, immunodominant surface-anchored GAS M proteins are polymorphic (>200 emm genotypes) (McMillan et al, 2013)and regions of their dimeric coiled-coil structure may provokean autoimmune response against cardiac tissue in rheumatic fever (Fae et al, 2005). Due to its prominence in the GAS cell wall and its conservation across all GAS strains, the GAC has been considered as a potential antigen for a universal GAS vaccine.…”

Section: Introductionmentioning

confidence: 99%

The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

Sorge

Cole

Kuipers

et al. 2014

Cell Host & Microbe

125

251

View full text Add to dashboard Cite

SUMMARY Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes,gacA-L. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAcside chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis and its understanding has implications for vaccine development.

show abstract

“…In the valves, we found several T cell oligoclonal populations defined by the analysis of the TCR (32, 33) that recognized M protein peptides from the N-terminal region and human cardiac myosin beta-chain peptides, as mentioned above, as well as valve tissue-derived proteins (31), as summarized in Figure 1. Among the valve proteins, we identified vimentin and disulfide isomerase ER-60 precursor (PDIA3) protein and a 78-kDa glucose-regulated protein precursor (HSPA5) as targets of the autoimmune reactions (34). It is interesting to note that apparently the recognition by T cells occurs in a cascade of reactivity from the myocardium to the valves.…”

Section: Heart Valve Chronic Inflammationmentioning

confidence: 99%

Rheumatic Heart Disease: Molecules Involved in Valve Tissue Inflammation Leading to the Autoimmune Process and Anti-S. pyogenes Vaccine

Guilherme

Kalil

2013

Front. Immunol.

View full text Add to dashboard Cite

The major events leading to both rheumatic fever (RF) and rheumatic heart disease (RHD) are reviewed. Several genes are involved in the development of RF and RHD. The inflammatory process that results from S. pyogenes infection involves the activation of several molecules such as VCAM and ICAM, which play a role in the migration of leukocytes to the heart, particularly to the valves. Specific chemokines, such as CXCL3/MIP1α as well as CCL1/I-309 and CXCL9/Mig, attract T cells to the myocardium and valves, respectively. The autoimmune reactions are mediated by both the B- and T-cell responses that begin at the periphery, followed by the migration of T cell clones to the heart and the infiltration of heart lesions in RHD patients. These cells recognize streptococcal antigens and human-tissue proteins. Molecular mimicry between streptococcal M protein and human proteins has been proposed as the triggering factor leading to autoimmunity in RF and RHD. The production of cytokines from peripheral and heart-infiltrating mononuclear cells suggests that T helper 1 and Th17 cytokines are the mediators of RHD heart lesions. The low numbers of IL-4 producing cells in the valvular tissue might contribute to the maintenance and progression of the valve lesions. The identification of a vaccine epitope opens a perspective of development of an effective and safe vaccine to prevent S. pyogenes infections, consequently RF and RHD.

show abstract

How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease

Cited by 46 publications

References 37 publications

Autoimmune Valvular Carditis

Autoimmune Valvular Carditis

The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

Rheumatic Heart Disease: Molecules Involved in Valve Tissue Inflammation Leading to the Autoimmune Process and Anti-S. pyogenes Vaccine

Contact Info

Product

Resources

About