Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease

Zhang, Yin; Zhao, Heru; Liu, Bin; Li, Li; Zhang, Lulu; Bao, Mei; Ji, Xinyu; He, Xiaojuan; Yi, Jianfeng; Chen, Peng; Lü, Cheng; Lu, Aiping

doi:10.3389/fphar.2020.00195

Cited by 17 publications

(7 citation statements)

References 41 publications

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“…The expression levels of eight known CHD‐related proteins, including heat shock protein HSP 90‐alpha (HSP90AA1) (Sevim Bayrak et al , 2020; Xiao et al , 2020), malate dehydrogenase (MDH2) (Liu et al , 2014), MYL9 (Xiong et al , 2019), ACLY (Ference et al , 2019), N‐ethylmaleimide sensitive factor (NSF) (Mei et al , 2020), α‐tropomyosin gene (TPM) (Hirono et al , 2020; Zhang et al , 2020), SERPINE1 (Song et al , 2017), and complement factor H related 2 (CFHR2) (Zhang et al , 2016) were altered consistently in both groups. The protein expression levels of HSP90AA1, MDH2, MYL9, and ACLY were higher in the CHD group than those in the control group.…”

Section: Resultsmentioning

confidence: 99%

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

Yin,

Cao,

Wang

et al. 2023

EMBO Mol Med

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Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

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Section: Resultsmentioning

confidence: 99%

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

Yin,

Cao,

Wang

et al. 2023

EMBO Mol Med

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“…Antibodies that cross-react with PRKG1 may also alter calcium levels, thus affecting TPM function. For TPM1, cross-reactive Spike antibodies targeting the ELDKY motif may result in coronary heart disease, as low-level autoantibodies against this protein have been associated with increased risk for this condition [ 78 ] and TPM1 and TPM3 are cardiac disease-linked antigens [ 77 ]. Cardiac disease, including myocardial injury and arrhythmia, can be induced by SARS-CoV-2 infection [ 79 ] and myocarditis has been found to develop in some individuals following vaccination against SARS-CoV-2 [ 80 ].…”

Section: Resultsmentioning

confidence: 99%

Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

Nunez-Castilla

Stebliankin

Baral

et al. 2022

Viruses

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Molecular mimicry between viral antigens and host proteins can produce cross-reacting antibodies leading to autoimmunity. The coronavirus SARS-CoV-2 causes COVID-19, a disease curiously resulting in varied symptoms and outcomes, ranging from asymptomatic to fatal. Autoimmunity due to cross-reacting antibodies resulting from molecular mimicry between viral antigens and host proteins may provide an explanation. Thus, we computationally investigated molecular mimicry between SARS-CoV-2 Spike and known epitopes. We discovered molecular mimicry hotspots in Spike and highlight two examples with tentative high autoimmune potential and implications for understanding COVID-19 complications. We show that a TQLPP motif in Spike and thrombopoietin shares similar antibody binding properties. Antibodies cross-reacting with thrombopoietin may induce thrombocytopenia, a condition observed in COVID-19 patients. Another motif, ELDKY, is shared in multiple human proteins, such as PRKG1 involved in platelet activation and calcium regulation, and tropomyosin, which is linked to cardiac disease. Antibodies cross-reacting with PRKG1 and tropomyosin may cause known COVID-19 complications such as blood-clotting disorders and cardiac disease, respectively. Our findings illuminate COVID-19 pathogenesis and highlight the importance of considering autoimmune potential when developing therapeutic interventions to reduce adverse reactions.

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“…Antibodies that cross-react with PRKG1 may also alter calcium levels, thus affecting TPM function. For TPM1, cross-reactive Spike antibodies targeting the ELDKY motif may result in coronary heart disease, as low-level autoantibodies against this protein have been associated with increased risk for this condition (Zhang et al, 2020) and TPM1 and TPM3 are cardiac disease-linked antigens (Marrama et al, 2022). Cardiac disease, including myocardial injury and arrhythmia, can be induced by SARS-CoV-2 infection (Nishiga et al, 2020) and myocarditis has been found to develop in some individuals following vaccination against SARS- CoV-2 (Patone et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Potential autoimmunity resulting from molecular mimicry between SARS-CoV-2 Spike and human proteins

Nunez-Castilla

Stebliankin

Baral

et al. 2021

Preprint

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Thrombocytopenia, characterized by reduced platelet count, increases mortality in COVID-19 patients. We performed a computational investigation of antibody-induced cross-reactivity due to molecular mimicry between SARS-CoV-2 Spike protein and human thrombopoietin, the regulator of platelet production, as a mechanism for thrombocytopenia in COVID-19 infections. The presence of a common sequence motif with similar structure and antibody-binding properties for these proteins strongly indicate shared molecular mimicry. Recent reports of antibodies in COVID-19 patients and pre-pandemic samples against epitopes containing the motif offer additional support for the cross-reactivity. Altogether, this suggests cross-reactivity between an antibody with affinity for Spike protein and a human protein. Consideration of cross-reactivity for SARS-CoV-2 is important for therapeutic intervention and when designing the next generation of COVID-19 vaccines to avoid potential autoimmune interference.

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Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease

Cited by 17 publications

References 41 publications

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

Potential autoimmunity resulting from molecular mimicry between SARS-CoV-2 Spike and human proteins

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