Human herpesvirus 6-induced inflammatory cardiomyopathy in immunocompetent children

Reddy, Sahitya; Eliassen, Eva; Krueger, G. R. F.; Das, Bibhuti B.

doi:10.4103/apc.apc_54_17

Cited by 14 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The clinical significance of this finding is not yet clear. On one hand, HHV6 has been linked to cardiac functional impairment [27], especially in children experiencing primary systemic active HHV6 infection where virus particles were detected in the endothelium [28]. Thus, it is well accepted that systemic HHV6 infection with high levels of HHV6 and viremia can induce acute myocarditis.…”

Section: Discussionmentioning

confidence: 99%

The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention

Elsanhoury

Kühl

Stautner

et al. 2022

Viruses

View full text Add to dashboard Cite

Introduction: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. Results: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (n = 79) of which 62% (n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3–12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and ‑negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. Conclusion: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials.

show abstract

Section: Discussionmentioning

confidence: 99%

The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention

Elsanhoury

Kühl

Stautner

et al. 2022

Viruses

View full text Add to dashboard Cite

show abstract

“…Moreover, the virus was associated with a risk of developing perimyocarditis and vasculitis. 14 Lysis of infected cells leads to increased numbers of autoantigens, enhancing the risk of autoimmunity in predisposed individuals. 15…”

Section: Discussionmentioning

confidence: 99%

Take a Second Look: It's Kikuchi’s Disease! A Case Report and Review of Literature

Joean

Thiele

Raap

et al. 2018

Clinics and Practice

View full text Add to dashboard Cite

Generalized lymphadenopathy is a common cause of concern for both patients and clinicians. Possible etiologies include infections, malignancies and autoimmune diseases. Kikuchi Fujimoto disease (KFD) is a hyperergic condition that presents with fever, lymphadenopathy and can include systemic involvement, thus being easily mistaken for the above-mentioned entities. We report the case of a previously healthy 18- year old male who presented with a selflimiting generalized lymphadenopathy, high fevers, skin vasculitis and polyserositis. The lymph-node biopsy revealed a histiocytotic necrotizing lymphadenitis, suggestive of Kikuchi’s disease. This case emphasizes the importance of KFD in the differential diagnosis of lymphadenopathy, especially in young adults.

show abstract

“…Various infectious and non-infectious causes have been implicated in the development of myocarditis, with viruses being the commonly suspected agents of the disease [ 1 , 2 , 3 , 4 ]. Historically, enteroviruses and adenoviruses were believed to be the key triggers of myocarditis in North America and Europe, respectively [ 5 , 6 ], but this trend is changing as other viruses, such as human herpesvirus-6 and parvovirus-19, are increasingly being reported as triggers, with the recent addition to the list being severe acute respiratory syndrome coronavirus-2 [ 7 , 8 , 9 ]. Mechanistically, different viruses cause tissue destruction by different pathways, but all appear to have a common outcome: DCM.…”

Section: Introductionmentioning

confidence: 99%

PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis

Rasquinha

Lasrado

Petro-Turnquist

et al. 2022

Biology

View full text Add to dashboard Cite

Enteroviruses such as group B coxsackieviruses (CVB) are commonly suspected as causes of myocarditis that can lead to dilated cardiomyopathy (DCM), and the mouse model of CVB3 myocarditis is routinely used to understand DCM pathogenesis. Mechanistically, autoimmunity is suspected due to the presence of autoantibodies for select antigens. However, their role continues to be enigmatic, which also raises the question of whether the breadth of autoantibodies is sufficiently characterized. Here, we attempted to comprehensively analyze the autoantibody repertoire using Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a versatile and high-throughput platform, in the mouse model of CVB3 myocarditis. First, PhIP-Seq analysis using the VirScan library revealed antibody reactivity only to CVB3 in the infected group but not in controls, thus validating the technique in this model. Second, using the mouse peptide library, we detected autoantibodies to 32 peptides from 25 proteins in infected animals that are ubiquitously expressed and have not been previously reported. Third, by using ELISA as a secondary assay, we confirmed antibody reactivity in sera from CVB3-infected animals to cytochrome c oxidase assembly factor 4 homolog (COA4) and phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), indicating the specificity of antibody detection by PhIP-Seq technology. Fourth, we noted similar antibody reactivity patterns in CVB3 and CVB4 infections, suggesting that the COA4- and PIK3AP1-reactive antibodies could be common to multiple CVB infections. The specificity of the autoantibodies was affirmed with influenza-infected animals that showed no reactivity to any of the antigens tested. Taken together, our data suggest that the autoantibodies identified by PhIP-Seq may have relevance to CVB pathogenesis, with a possibility that similar reactivity could be expected in human DCM patients.

show abstract

Human herpesvirus 6-induced inflammatory cardiomyopathy in immunocompetent children

Cited by 14 publications

References 40 publications

The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention

The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention

Take a Second Look: It's Kikuchi’s Disease! A Case Report and Review of Literature

PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis

Contact Info

Product

Resources

About