Quantitative determination of IgM antibodies reduces the pitfalls in the serodiagnosis of tick-borne encephalitis

Stiasny, Karin; Aberle, Judith H.; Chmelík, V; Karrer, Urs; Holzmann, Heidemarie; Heinz, Franz X.

doi:10.1016/j.jcv.2012.02.016

Cited by 39 publications

(36 citation statements)

References 35 publications

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“…Since TBEV and WNV infections both display very similar clinical pictures, distinguishing between WNV and TBEV antibodies will be frequently required in routine diagnostic practice. The present and previous studies of our group [23] as well as others [24], however, indicate that the extent of cross-reactivity between the two viruses -especially in IgM assaysis so low that distinguishing between recent infections is usually unproblematic.…”

Section: Discussioncontrasting

confidence: 46%

Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections

2013

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human WNV infections have not previously been documented, although the virus was isolated from birds and detected in mosquitoes in 2008 and 2009. We therefore conducted a retrospective search for human cases of WNV infection using serum and cerebrospinal fluid samples collected from patients with central nervous system (CNS) disease in the summers of 2009, 2010 and 2011. Although all samples were negative for WNV by polymerase chain reaction, quantitative evaluation of standardised antibody assays with purified flavivirus antigens (including Usutu virus, which cross-reacts with WNV even in neutralisation assays) provided serological evidence for three autochthonous WNV infections in Austria: two in 2009 and one in 2010. Our data highlight the importance of raising awareness of WNV infections in Austria and neighbouring countries and suggest including testing for this infection in routine diagnostic practice of CNS diseases.

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Section: Discussioncontrasting

confidence: 46%

Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections

2013

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“…TBEv‐specific antibody titers were measured before (week 0), during (week 8), and after (week 28) the TBEv vaccination course by ELISA and TBEv‐neutralization according to published protocols (Stiasny et al ., 2012). The TBEv‐specific cellular immune response was assessed at weeks 0 and 26 by IFN‐γ enzyme‐linked immunosorbent spot (ELISpot) assay using pools of overlapping peptides for all structural proteins of TBEv.…”

Section: Methodsmentioning

confidence: 99%

Reduced naïve CD 8 ⁺ T ‐cell priming efficacy in elderly adults

et al. 2015

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SummaryAging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8+ T‐cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8+ T‐cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8+ T‐cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8+ T‐cell responses specific for a model antigen. Reduced CD8+ T‐cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8+ T‐cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging.

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“…For such patients, higher sensitivity at the expense of specificity might be warranted, in order to avoid missed diagnoses. However, the search for less specific IgM in the acute second phase of TBE is not without problems (19), due to partly overlapping clinical presentations of other flavivirus infections, the increased potential of cross-reactivity, and the increasing risk of exposure to other flaviviruses through travel and now autochthonous transmission within Europe (20)(21)(22). This raises questions about confirmatory testing strategies.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays

Weissbach¹,

Hirsch²

2015

Clin. Vaccine Immunol.

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Despite the availability of protective vaccines, tick-borne encephalitis virus (TBEV) infections have been increasingly reported to the European Centre for Disease Prevention and Control in the past 2 decades. Since the diagnosis of TBEV exposure relies on serological testing, we compared two commercial enzyme-linked immunosorbent assays (ELISAs), i.e., Immunozym FSME IgG assay (ELISA-1) and Euroimmun FSME Vienna IgG assay (ELISA-2). Both assays use whole TBEV antigens, but they differ in viral strains (Neudoerfl for ELISA-1 and K23 for ELISA-2) and cutoff values. In testing of samples from 398 healthy blood donors, ELISA-1 showed higher reactivity levels than ELISA-2 (P < 0.001), suggesting different assay properties. This finding was supported by Bland-Altman analysis of the optical density at 450 nm (OD 450 ) (mean bias, ؉0.32 [95% limits of agreement, ؊0.31 to ؉0.95]) and persisted after transformation into Vienna units. Concordant results were observed for 276 sera (69%) (44 positive and 232 negative results). Discordant results were observed for 122 sera (31%); 15 were fully discordant, all being ELISA-1 positive and ELISA-2 negative, and 107 were partially discordant (101 being ELISA-1 indeterminate and ELISA-2 negative and 6 having positive or indeterminate reactivity in both ELISAs). Neutralization testing at a 1:10 dilution yielded positive results for 33 of 44 concordant positive sera, 1 of 15 fully discordant sera, and 1 of 33 partially discordant sera. Indirect immunofluorescence testing revealed high antibody titers of >100 for yellow fever virus in 18 cases and for dengue virus in one case, suggesting that cross-reactivity contributed to the ELISA-1 results. We conclude that (i) cross-reactivity among flaviviruses remains a limitation of TBEV serological testing, (ii) ELISA-2 revealed reasonable sensitivity and specificity for anti-TBEV IgG population screening of human sera, and (iii) neutralization testing is most specific and should be reserved for selective questions. Despite the availability of protective vaccines, tick-borne encephalitis (TBE) has been increasingly reported in Europe over the past 2 decades (1). According to a recent analysis by the European Centre for Disease Prevention and Control (ECDC), 29,381 cases of TBE have been diagnosed in 16 countries of the European Union (EU)/European Free Trade Association (EFTA) since the year 2000. The annual rates range from 2,000 to 3,500 cases per year, showing a net increase despite a remarkable and as yet unexplained 3-year peak periodicity. Climate changes, with milder winters and earlier and prolonged summer seasons, and increasing numbers of small rodent and larger wild and domestic animal hosts, such as deer, sheep, and goats, are thought to contribute to expanding areas in which tick-borne encephalitis virus (TBEV)-infected ticks are endemic, which facilitates human exposure during occupational and leisure activities outdoors (2-4). The notable exception to this European trend is Austria, where TBEV vaccination has been effectively ...

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Quantitative determination of IgM antibodies reduces the pitfalls in the serodiagnosis of tick-borne encephalitis

Cited by 39 publications

References 35 publications

Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections

Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections

Reduced naïve CD 8 ⁺ T ‐cell priming efficacy in elderly adults

Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays

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Quantitative determination of IgM antibodies reduces the pitfalls in the serodiagnosis of tick-borne encephalitis

Cited by 39 publications

References 35 publications

Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections

Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections

Reduced naïve CD 8 + T ‐cell priming efficacy in elderly adults

Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays

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Reduced naïve CD 8 ⁺ T ‐cell priming efficacy in elderly adults