Measurement of Organ-Specific and Acute-Phase Blood Protein Levels in Early Lyme Disease

Lyme disease results from infection
of humans with the spirochete Borrelia burgdorferi. The first and most common clinical
manifestation is the circular, inflamed skin lesion referred to as
erythema migrans; later manifestations result from infections of other
body sites. Laboratory diagnosis of Lyme disease can be challenging
in patients with erythema migrans because of the time delay in the
development of specific diagnostic antibodies against Borrelia. Reliable blood biomarkers for the early diagnosis of Lyme disease
in patients with erythema migrans are needed. Here, we performed selected
reaction monitoring, a targeted mass spectrometry-based approach,
to measure selected proteins that (1) are known to be predominantly
expressed in one organ (i.e., organ-specific blood proteins) and whose
blood concentrations may change as a result of Lyme disease, or (2)
are involved in acute immune responses. In a longitudinal cohort of
40 Lyme disease patients and 20 healthy controls, we identified 10
proteins with significantly altered serum levels in patients at the
time of diagnosis, and we also developed a 10-protein panel identified
through multivariate analysis. In an independent cohort of patients
with erythema migrans, six of these proteins, APOA4, C9, CRP, CST6,
PGLYRP2, and S100A9, were confirmed to show significantly altered
serum levels in patients at time of presentation. Nine of the 10 proteins
from the multivariate panel were also verified in the second cohort.
These proteins, primarily innate immune response proteins or proteins
specific to liver, skin, or white blood cells, may serve as candidate
blood biomarkers requiring further validation to aid in the laboratory
diagnosis of early Lyme disease.