Intrathecal IgM, IgA and IgG antibody response in tick-borne encephalitis. Long-term follow-up related to clinical course and outcome

Background: Tick-borne encephalitis (TBE) of western subtype causes long-term morbidity and is considered a health problem in Scandinavia, eastern and central parts of Europe and Russia. The pathophysiology is not fully elucidated. As TBE RNA is rarely demonstrable in cerebrospinal fluid (CSF) the kinetics of the CSF antibody response to the disease has attracted attention.

Objectives: To investigate the intrathecal TBE-specific antibody response and to correlate its intensity and persistence to the clinical course. To compare indirect, commercially-based ELISA methods indexed against albumin ratio or IgG ratio with the capture ELISA method for the establishment of CSF response.

Study design: The specific IgM, IgG and IgA antibody responses in serum and CSF were analysed in 69 Swedish patients included in a prospective study of TBE from the acute phase up to 11 – 13 months after onset.

Results: Antibody 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 early during the disease and persisted after 6 weeks. Maximum IgG levels were encountered in late convalescent samples (median 6 weeks). Intrathecal antibody production was demonstrable in nearly all patients: in 41% days 0–6, in 97% days 7–19, in 98% days 21–61 and—at lower levels—in 84% of the patients after 1 year ($\text{50}\text{52}$ of CSF-serum sampled in the interval 11–61 days). Day 9 after onset, patients with dominating encephalitic symptoms showed significantly lower intrathecal IgM activity. The persistence of serum and CSF antibodies did not correlate to severity of disease.

Conclusions: Capture IgM and IgG assays were superior to indirect ELISA. Low early CSF IgM response correlated to encephalitic symptoms, otherwise the intensity and duration of intrathecal antibody response were of limited value for the prediction of clinical course and long-term outcome.