Early and late antibody responses to full-length and truncated constructs of outer surface protein A of Borrelia burgdorferi in Lyme disease

Abstract

The immunoglobulin G (IgG) antibody response to outer surface protein A (OspA) of Borrelia burgdorferi has been reported to occur late in the course of Lyme disease. To learn when reactivity to particular epitopes of OspA develops and whether the strength of particular responses correlates with the duration of arthritis and HLA-DR specificities, we determined the IgM and IgG responses by enzyme-linked immunosorbent assay in 128 patients with various manifestations of Lyme disease to full-length recombinant OspA and three OspA fragments which divided the protein approximately into thirds. Among the 10 patients who were followed serially, an early IgM response was often found to epitopes in all three fragments of OspA, sometimes accompanied by a weak IgG response, primarily to an epitope in the middle third of the protein. Months to years later, the seven patients who had prolonged or moderate episodes of arthritis developed strong IgG responses to OspA, especially to epitopes in the N-terminal and C-terminal fragments, that paralleled the course of the arthritis. In single serum samples from 128 patients, a similar pattern of IgM and IgG reactivity with OspA epitopes was seen in patients with early or late manifestations of the illness. Of the 80 patients with arthritis, 62 (78%) had IgG responses to OspA, usually with the strongest reactivity to the C-terminal fragment. In these patients, the strength of the IgG response to OspA correlated with the duration of arthritis; in HLA-DR4-positive patients, most of whom had chronic arthritis, this association was attributable to reactivity with the C-terminal fragment. Thus, patients with Lyme disease often have early responses to OspA, but those with prolonged arthritis do not develop IgG responses to certain epitopes of the protein until late in the illness. In patients with HLA-DR4, the strength of IgG reactivity with one or more epitopes in the C-terminal fragment of OspA correlates with the duration of arthritis.