Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis

Abstract

Tick-borne encephalitis (TBE) is associated with a range of disease severity. The reasons for this heterogeneity are not clear. Levels of serum IgG antibodies to TBE virus (TBEV) were determined in 691 adult patients during the meningoencephalitic phase of TBE and correlated with detailed clinical and laboratory parameters during acute illness and with the presence of post-encephalitic syndrome (PES) 2–7 years after TBE. Specific IgG antibody levels ranged from below cut-off value (in 32/691 patients, 4.6%), to 896 U/mL (median = 37.3 U/mL). Patients with meningoencephalomyelitis were more often seronegative (24.3%; 9/37) than those with meningoencephalitis (4.7%; 20/428) or meningitis (1.3%; 3/226). Moreover, patients with antibody levels below cut-off had longer hospitalization (13 versus 8 days); more often required intensive care unit treatment (22% versus 8%) and artificial ventilation (71% versus 21%); and had a higher fatality rate (3/32; 9.4% versus 1/659; 0.2%) than seropositive patients. These results were confirmed when antibody levels, rather than cut-off values, were correlated with clinical parameters including the likelihood to develop PES. Low serum IgG antibody responses against TBEV at the onset of neurologic involvement are associated with a more difficult clinical course and unfavorable long-term outcome of TBE, providing a diagnostic and clinical challenge for physicians.

Poor virus-specific T-cell responses early after tick-borne encephalitis virus infection correlate with disease severity

“…Animal models have demonstrated that virus-specific antibodies contribute to protective immunity against TBEV infections [ 13 , 17–21 ]. Also in humans, TBEV-specific antibodies have been identified as a correlate of protection [ 6 ]. In the latter study, low or undetectable virus-specific IgG antibody levels early in the course of TBE, correlated with disease severity and unfavorable long-term disease outcomes [ 6 ].…”

“…Also in humans, TBEV-specific antibodies have been identified as a correlate of protection [ 6 ]. In the latter study, low or undetectable virus-specific IgG antibody levels early in the course of TBE, correlated with disease severity and unfavorable long-term disease outcomes [ 6 ]. In the present study, we extended analysis of the antibody responses and tested TBEV-specific IgG and IgM antibodies, VN antibody titers (VNT 100 ), TBEV E-domain III (EDIII)- and NS1-specific antibodies in serum samples of subjects of which also T-cell data were obtained.…”

“…Previous studies showed that poor virus-neutralizing antibody responses are associated with severe disease and clinical outcome of TBE [ 6 , 7 ]. Upon infection with TBEV, stronger antibody responses to the E and NS1 proteins are induced than after vaccination [ 2 , 32 ].…”

“…Viruses of the European TBEV subtype typically cause a biphasic course of disease, with an initial viraemic phase associated with non-specific symptoms such as fever, malaise, fatigue and headache, followed by a brief asymptomatic period and a second phase in which patients may remain asymptomatic or present with neurological disease. Neuronal TBE manifestations may include meningitis, meningoencephalitis or meningoencephalomyelitis [ 4 , 6–8 ]. Importantly, long-term post-encephalitic sequelae can occur in about a third of symptomatic TBE cases [ 9 ].…”

Selected Biomarkers of Tick-Borne Encephalitis: A Review

“…On the other hand, 5% of patients that are seronegative have more severe illness, i.e., seronegativity is approximately 20 times higher in patients with meningoencephalomyelitis in comparison to those with meningitis. Moreover, it is associated with the presence of postencephalitic syndrome following infection [ 44 ].…”