To the Editor—We thank Naktin for his letter [1] regarding our recently published study in Clinical Infectious Diseases [2] in which we examined the expression of acute phase response proteins in patients with various manifestations of Lyme disease. Naktin expressed concern over the extrapolation that was made regarding the level of anti-Borrelia burgdorferi antibody based on the optical density (OD) signal measured in the enzyme-linked immunosorbent assay. However, this is considered a valid measure of the antibody response and has been used extensively in other research studies on Lyme disease [3–6]. To examine the relationship between anti-B. burgdorferi antibody titer and OD, we tested serum from 20 representative patients with Lyme disease. As can be seen in the accompanying Figure 1, there was a strong correlation between titer and OD (r = 0.953, P < .0001; Spearman correlation). Because of the 1:2 serial dilutions often used to determine antibody titer, OD values generally offer a more quantitative measure of antibody response when the detected signal is in the assay’s linear range. We agree with Naktin that it has not been established that knowledge of the magnitude of the humoral immunologic response to B. burgdorferi has clinical utility.
Correlation between anti-Borrelia burgdorferi antibody titer and optical density at 450 nm, as measured by enzyme-linked immunosorbent assay. Abbreviation: OD, optical density.
We included information on the level of the immunoglobulin G (IgG) antibody response to B. burgdorferi in our article for a number of reasons. It has been previously demonstrated by our group and others that, during Lyme disease, serum IgG antibodies to B. burgdorferi are at their lowest levels in early infection in patients with erythema migrans and increase as the spirochete disseminates to extracutaneous sites and the infection progresses to later stages [3, 7–9]. An important aspect of the current study pertained to the relationship between the stage of infection and the expression of C-reactive protein (CRP). The data showed that the CRP response is highest in early Lyme disease, when serum levels of IgG antibody to B. burgdorferi are comparatively low, and subsides after dissemination of the organism and its clearance from blood, when a robust IgG response to B. burgdorferi has developed. Another reason for the presentation and analysis of the anti-B. burgdorferi antibody response was related to the comparison between patients with post-treatment Lyme disease syndrome (PTLDS) and the post-treatment Lyme disease healthy (PTLDH) controls, that is, individuals with a history of Lyme disease who were not experiencing persistent symptoms following antibiotic treatment. Our findings indicated that there is a significantly elevated expression of CRP in PTLDS patients, despite the fact that neither the IgG anti-B. burgdorferi antibody response nor the stage of infection when antibiotic treatment was given differed significantly between the PTLDS and PTLDH cohorts. This and other data from the study were interpreted as suggestive of distinct underlying mechanisms for the observed increase in CRP expression in active Lyme disease vs PTLDS.
Disclaimer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Financial support. This work was supported by the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) grants R56AI093763 (A. A.) and U54AI057158 (Northeast Biodefense Center-Lipkin) (A. A.), the Global Lyme Alliance (A. A.), and the Intramural Research Program of NIAID (A. R. M.).
Potential conflicts of interest. G. P. W. reports receiving research grants from Immunetics, Inc.; the Institute for Systems Biology; Rarecyte, Inc.; and Quidel Corporation. He owns equity in Abbott; has been an expert witness in malpractice cases involving Lyme disease and babesiosis; and is an unpaid board member of the American Lyme Disease Foundation. A. R. M. is a coinventor on a US patent using the luciferase immunoprecipitation systems assay for profiling antibody responses to a panel of B. burgdorferi proteins. A. A. reports receiving grants from the NIH and the Global Lyme Alliance for research related to Lyme disease. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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Author notes
Correspondence: A. Alaedini, Department of Medicine, Columbia University Medical Center, 1130 Saint Nicholas Ave., 9th Floor, New York, NY 10032 (aa819@columbia.edu).
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