False-negative serology in patients with neuroborreliosis and the value ofemploying of different borrelial strains in serological assays

The risk of obtaining false-negative results in serological assays in serum and CSF specimens with only one strain of Borrelia burgdorferi sensu Into as antigen was investigated in 79 patients with neuroborreliosis with speci mens obtained at initial presentation. Serum antibodies were assessed by im munoblotting; the criteria of Hauser et al. were used to evaluate the test. The intrathecal synthesis of borrelial-specific IgM and IgG antibodies was examined by enzyme immunoassay (EIA). Strains of B. burgdorferi sensu stri cto (BbZ160), B. garinii (Bbii50) and B. afzelii (PKO) served as sources of antigen in both assays. All patients produced either a positive IgM or IgG test in serum with at least one strain of B. burgdorferi sensu lato. React ivity of IgM or IgC antibodies, or both, with antigens of all three strains was demonstrated in 67 (85%) of 79 sera. The correlation of results of imm unoblotting with different strains was significantly better for IgG (85%) t han for IgM antibodies (54%). The variability of positive IgM reactions in 18 specimens was mainly due to the fact that the antibodies were directed t o the relevant variable outer-surface protein C (p23). Intrathecal synthesi s of IgG antibodies was demonstrated in 58 patients (81%) of 72 and of IgM antibodies in 25 of 58 patients. No patient had isolated intrathecal synthe sis of IgM antibodies. The majority of CSF samples (56 of 58) were assessed as IgG antibody-positive, independent of the borrelial strain used as anti gen in EIA, whereas only 10 of 25 IgM antibody-positive CSF specimens react ed with all three strains. All patients in the study had intrathecal antibo dy synthesis demonstrable at 6-week follow-up. From this study it is conclu ded that there is a small, but real, risk of false-negative serological fin dings at the time of initial clinical presentation in patients with typical symptoms of neuroborreliosis. In these patients a negative serological res ult with one strain should prompt the repetition of the test with other str ains of B. burgdorferi sensu lato.