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

Authors

Yong Zhou
Shizhen Qin
Mingjuan Sun
Li Tang
Xiaowei Yan
Taek-Kyun Kim
Juan Caballero
Gustavo Glusman
Mary E. Brunkow
Mark J. Soloski
Alison W. Rebman
Carol Scavarda
Denise Cooper
Gilbert S. Omenn
Robert L. Moritz
Gary P. Wormser, New York Medical CollegeFollow
Nathan D. Price
John N. Aucott
Leroy Hood

DOI

10.1021/acs.jproteome.9b00569

Journal Title

Journal of Proteome Research

First Page

346

Last Page

359

Document Type

Article

Publication Date

1-3-2020

Department

Medicine

Abstract

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.

Recommended Citation

Zhou, Y., Qin, S., Sun, M., Tang, L., Yan, X., Kim, T., Caballero, J., Glusman, G., Brunkow, M. E., Soloski, M. J., Rebman, A. W., Scavarda, C., Cooper, D., Omenn, G. S., Moritz, R. L., Wormser, G. P., Price, N. D., Aucott, J. N., & Hood, L. (2020). Measurement of Organ-Specific and Acute-Phase Blood Protein Levels in Early Lyme Disease. Journal of Proteome Research, 19 (1), 346-359. https://doi.org/10.1021/acs.jproteome.9b00569