Key result
Group A streptococci and coxsackie viruses exhibit significant molecular mimicry and antibody cross-reactivity with extracellular cardiac proteins like laminin and collagen IV.
Extracellular cardiac proteins such as laminin, collagen IV, CAR, and B1AR may be the initial targets of molecular mimicry in rheumatic heart disease and autoimmune myocarditis.
Hypothesis-generating for autoimmune cardiac targets; does not support clinical practice changes pending human studies.
RATIONALE: Molecular mimicry theory (MMT) suggests that epitope mimicry between pathogens and human proteins can activate autoimmune disease. Group A streptococci (GAS) mimics human cardiac myosin in rheumatic heart disease (RHD) and coxsackie viruses (CX) mimic actin in autoimmune myocarditis (AM). But myosin and actin are immunologically inaccessible and unlikely initial targets. Extracellular cardiac proteins that mimic GAS and CX would be more likely. OBJECTIVES: To determine whether extracellular cardiac proteins such as coxsackie and adenovirus receptor (CAR), beta 1 adrenergic receptor (B1AR), CD55/DAF, laminin, and collagen IV mimic GAS, CX, and/or cardiac myosin or actin. METHODS: BLAST 2.0 and LALIGN searches of the UniProt protein database were employed to identify potential molecular mimics. Quantitative enzyme-linked immunosorbent assay was used to measure antibody cross-reactivity. MEASUREMENTS: Similarities were considered to be significant if a sequence contained at least 5 identical amino acids in 10. Antibodies were considered to be cross-reactive if the binding constant had a K d less than 10(-9) M. MAIN RESULTS: Group A streptococci mimics laminin, CAR, and myosin. CX mimics actin and collagen IV and B1AR. The similarity search results are mirrored by antibody cross-reactivities. Additionally, antibodies against laminin recognize antibodies against collagen IV; antibodies against actin recognize antibodies against myosin, and antibodies against GAS recognize antibodies against CX. Thus, there is both mimicry of extracellular proteins and antigenic complementarity between GAS-CX in RHD/AM. CONCLUSION: Rheumatic heart disease/AM may be due to combined infections of GAS with CX localized at cardiomyocytes that may produce a synergistic, hyperinflammatory response that cross-reacts with laminin, collagen IV, CAR, and/or B1AR. Epitope drift shifts the immune response to myosin and actin after cardiomyocytes become damaged.
No takes yet. Share an insight, caveat, or question.
Robert Root‐Bernstein (2014) studied Rheumatic heart disease and autoimmune myocarditis. In vitro molecular mimicry analysis was evaluated on Sequence similarity and antibody cross-reactivity between pathogens (GAS, CX) and extracellular cardiac proteins. Group A streptococci and coxsackie viruses exhibit significant molecular mimicry and antibody cross-reactivity with extracellular cardiac proteins like laminin and collagen IV.