Laboratory testing for the diagnosis of
Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the
infection. Serodiagnostic assays to detect the early stages of
infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi
proteins known to be induced within feeding ticks and/or during mammalian
infection for their utility as serodiagnostic markers against a comprehensive panel of
Lyme disease patient serum samples. The
antigens were assayed for
IgM and
IgG reactivity in line immunoblots and separately by
enzyme-linked
immunosorbent assay (ELISA), with a focus on reactivity against early
Lyme disease with
erythema migrans (EM), early disseminated
Lyme neuroborreliosis, and early Lyme
carditis patient serum samples. By
IgM immunoblotting, we found that
recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the
OspC antigen used in the current
IgM blotting criteria. Additionally, these
proteins reacted with serum samples from patients with early neuroborreliosis and early
carditis, suggesting value in detecting early stages of this
disease progression. We also found serological reactivity against
recombinant proteins BBA69 and BBA73 with early-
Lyme-disease samples using
IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the
antigens by
IgM/
IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed
antigens into the current
IgM/
IgG immunoblotting tier in a
recombinant protein platform assay may improve the performance of early-
Lyme-disease serologic testing.