HUMORAL IMMUNE-RESPONSE TO OUTER SURFACE PROTEIN-C OF BORRELIA-BURGDORFERI IN LYME-DISEASE - ROLE OF THE IMMUNOGLOBULIN-M RESPONSE IN THE SERODIAGNOSIS OF EARLY INFECTION

We determined the humoral immune response to outer surface protein C ( OspC) of Borrelia burgdorferi in patients with early or late manifesta tions of Lyme disease and investigated the use of this antigen in the serodiagnosis of early infection. The ospC gene from the low-passage h uman isolate 297, a North American B. burgdorferi strain, was used to make a recombinant maltose-binding protein (MBP)-OspC fusion protein f or serologic tests. This gene showed 84 to 85% nucleotide sequence ide ntity and 76 to 79% amino acid identity with ospC of B. burgdorferi B3 1 and 2591. The antibody responses to MBP-OspC were determined in seri al sera from 15 patients with Lyme disease who were monitored for 4 to 12 years of illness, in single-serum samples from 189 patients with e arly or late manifestations of the disorder, and in serum samples from 106 control patients. Early in the infection, patients with erythema migrans or meningitis commonly had weak to strong immunoglobulin M (Ig M) responses to OspC and sometimes weak to moderate IgG responses. Mon ths to years later, weak to strong IgG reactivity with this protein wa s often apparent in patients with arthritis, but this response was wea k or absent in patients with chronic neuroborreliosis. When acute and convalescent-phase serum samples from patients with erythema migrans w ere tested for reactivity against MBP-OspC, the sensitivity of the IgM test was 73% and the specificity was 98%, with either enzyme-linked i mmunosorbent assay (ELISA) or Western blotting. We conclude that the m ajority of patients with Lyme disease have a prominent IgM response to OspC early in the illness, which is often followed by a prominent IgG response in patients with arthritis. For the serodiagnosis of early i nfection, the sensitivity and specificity of IgM ELISA and Western blo tting were comparable or slightly improved when MBP-OspC was used as t he antigen compared with tests in which spirochetal lysates were used.