G. Gunther et al., INTRATHECAL IGM, IGA AND IGG ANTIBODY-RESPONSE IN TICK-BORNE ENCEPHALITIS - LONG-TERM FOLLOW-UP RELATED TO CLINICAL COURSE AND OUTCOME, Clinical and diagnostic virology, 8(1), 1997, pp. 17-29
Background: Tick-borne encephalitis (TBE) of western subtype causes lo
ng-term morbidity and is considered a health problem in Scandinavia, e
astern and central parts of Europe and Russia. The pathophysiology is
not fully elucidated. As TBE RNA is rarely demonstrable in cerebrospin
al fluid (CSF) the kinetics of the CSF antibody response to the diseas
e has attracted attention. Objectives: To investigate the intrathecal
TBE-specific antibody response and to correlate its intensity and pers
istence to the clinical course. To compare indirect, commercially-base
d ELISA methods indexed against albumin ratio ol IgG ratio with the ca
pture ELISA method for the establishment of CSF response. Study design
: The specific IgM, IgG and IgA antibody responses in serum and CSF we
re analysed in 69 Swedish patients included in a prospective study of
TEE from the acute phase up to 11-13 months after onset. Results: Anti
body response by all three classes was demonstrable in serum and CSF.
All methods were useful, but capture technique was the most sensitive
and results were easiest to interpret. Peak IgM activity was seen earl
y during the disease and persisted after 6 weeks. Maximum IgG levels w
ere encountered in late convalescent samples (median 6 weeks). Intrath
ecal antibody production was demonstrable in nearly all patients: in 4
1% days 0-6, in 97% days 7-19, in 98% days 21-61 and-at lower levels-i
n 84% of the patients after 1 year (50/52 of CSF-serum sampled in the
interval 11-61 days). Day 9 after onset, patients with dominating ence
phalitic symptoms showed significantly lower intrathecal IgM activity.
The persistence of serum and CSF antibodies did not correlate to seve
rity of disease. Conclusions: Capture IgM and IgG assays were superior
to indirect ELISA. Low early CSF Igm response correlated to encephali
tic symptoms, otherwise the intensity and duration of intrathecal anti
body response were of limited value for the prediction of clinical cou
rse and long-term outcome. (C) 1997 Elsevier Science B.V.