Enterovirus infections in young infants: Are children still protected by maternal antibodies?

Salur, Liina; Oikarinen, Sami; Tauriainen, Sisko; Mandel, Maire; Hyöty, Heikki; Uibo, Raivo

doi:10.4161/hv.7.9.16082

Cited by 10 publications

(7 citation statements)

References 30 publications

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“…These observations are also supported by data from Finland showing declining proportion of pregnant women containing antibodies to CBV4 from 1983 to 1995 [Viskari et al, 2000]. Similar findings have also been reported more recently from Estonia [Salur et al, 2011].…”

Section: Discussionsupporting

confidence: 86%

Frequency of enterovirus detection in blood samples of neonates admitted to hospital with sepsis‐like illness in Kuwait

Ahmad

Dalwai

Al‐Nakib

2013

Journal of Medical Virology

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This study investigated the role of enteroviruses in sepsis-like illness among neonates in Kuwait. Serum samples from 139 consecutive neonates presenting with sepsis-like illness during a three and a half-year-period whose blood cultures were negative for bacterial pathogens were tested. Enterovirus RNA was detected by single-step reverse-transcription PCR (RT-PCR). Specific genotypes were identified by direct DNA sequencing of enteroviral genome. Serotype-specific antibodies in serum samples from some selected patients were detected by virus neutralization test using coxsackievirus B types (CBVs). All 139 neonates presented with sepsis-like illness and blood samples were uniformly negative for aerobic/anaerobic bacterial cultures. Fifty-six (40%) neonates had further complications of sepsis including carditis (n = 34) and multi-organ involvement (n = 22). Enterovirus RNA was detected by RT-PCR in 34 of 139 (24%) serum samples which is among the highest frequency reported so far in non-epidemic settings. Genotyping identified CBVs as most common enteroviruses, causing 19 of 34 (56%) enteroviral sepsis episodes in neonates. Of 34 carditis cases, 18 were positive for CBVs by serotyping including all 10 enterovirus RNA-positive samples. Only one fatality was observed due to liver failure in a neonate with hepatitis. Our data showed that enteroviruses are responsible for 24% of neonatal sepsis cases due to non-bacterial causes in Kuwait. The data indicate that enteroviruses should be considered in the differential diagnosis of sepsis-like illness among neonates, particularly those with negative blood cultures for bacterial pathogens.

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Section: Discussionsupporting

confidence: 86%

Frequency of enterovirus detection in blood samples of neonates admitted to hospital with sepsis‐like illness in Kuwait

Ahmad

Dalwai

Al‐Nakib

2013

Journal of Medical Virology

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“…The cause of this immune response deficiency is unclear. For enteroviruses, poor protection from infection by inadequate maternal transfer of antibodies was suggested as a potential cause for increased infections in children who develop beta cell autoimmunity23. However, our findings of robust anti-VP1 antibodies in cord blood of the newborns who developed either insulin or GAD targeted autoimmunity did not support this hypothesis.…”

Section: Discussioncontrasting

confidence: 70%

Incomplete immune response to coxsackie B viruses associates with early autoimmunity against insulin

Ashton

Eugster

Walther

et al. 2016

Sci Rep

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Viral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely defined by different binding to VP1 or VP2. Antibody responses that were anti-VP2 competent but anti-VP1 deficient were unable to neutralize CVB, and were characteristic of children who developed early insulin-targeting autoimmunity, suggesting an impaired ability to clear CVB in early childhood. In contrast, children who developed a GAD-targeting autoimmunity had robust VP1 and VP2 antibody responses to CVB. We further found that 20% of memory CD4+ T cells responding to the GAD65247-266 peptide share identical T cell receptors to T cells responding to the CVB4 p2C30-51 peptide, thereby providing direct evidence for the potential of molecular mimicry as a mechanism for GAD autoimmunity. Here, we highlight functional immune response differences between children who develop insulin-targeting and GAD-targeting autoimmunity, and suggest that children who lose B cell tolerance to insulin within the first years of life have a paradoxical impaired ability to mount humoral immune responses to coxsackie viruses.

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“…This bottleneck cannot be ignored given the fact that enterovirus infections are common already before the age of 3 months [40]. The findings we present here offer a potential solution to the problem of poor vaccine efficacy in newborns by suggesting that maternal immunity is passively transferred to the offspring, providing immediate protection from infections.…”

Section: Discussionmentioning

confidence: 74%

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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Aims/hypothesis Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.Methods The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice. Results Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes. Conclusions/interpretation Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.

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Enterovirus infections in young infants: Are children still protected by maternal antibodies?

Cited by 10 publications

References 30 publications

Frequency of enterovirus detection in blood samples of neonates admitted to hospital with sepsis‐like illness in Kuwait

Frequency of enterovirus detection in blood samples of neonates admitted to hospital with sepsis‐like illness in Kuwait

Incomplete immune response to coxsackie B viruses associates with early autoimmunity against insulin

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

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