Antiphospholipid autoantibodies in Lyme disease arise after scavenging of host phospholipids by Borrelia burgdorferi
Peter J. Gwynne, … , Adriana R. Marques, Linden T. Hu
Peter J. Gwynne, … , Adriana R. Marques, Linden T. Hu
Published March 15, 2022
Citation Information: J Clin Invest. 2022;132(6):e152506. https://doi.org/10.1172/JCI152506.
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Antiphospholipid autoantibodies in Lyme disease arise after scavenging of host phospholipids by Borrelia burgdorferi

Abstract

A close association with its vertebrate and tick hosts allows Borrelia burgdorferi, the bacterium responsible for Lyme disease, to eliminate many metabolic pathways and instead scavenge key nutrients from the host. A lipid-defined culture medium was developed to demonstrate that exogenous lipids are an essential nutrient of B. burgdorferi, which can accumulate intact phospholipids from its environment to support growth. Antibody responses to host phospholipids were studied in mice and humans using an antiphospholipid ELISA. Several of these environmentally acquired phospholipids including phosphatidylserine and phosphatidic acid, as well as borrelial phosphatidylcholine, are the targets of antibodies that arose early in infection in the mouse model. Patients with acute infections demonstrated antibody responses to the same lipids. The elevation of antiphospholipid antibodies predicted early infection with better sensitivity than did the standardized 2-tier tests currently used in diagnosis. Sera obtained from patients with Lyme disease before and after antibiotic therapy showed declining antiphospholipid titers after treatment. Further study will be required to determine whether these antibodies have utility in early diagnosis of Lyme disease, tracking of the response to therapy, and diagnosis of reinfection, areas in which current standardized tests are inadequate.

Authors

Peter J. Gwynne, Luke H. Clendenen, Siu-Ping Turk, Adriana R. Marques, Linden T. Hu

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Figure 2

Uptake of fluorescence-labeled phospholipids by B. burgdorferi.

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Uptake of fluorescence-labeled phospholipids by B. burgdorferi. The cano...
The canonical phospholipids of B. burgdorferi PC and PG, as well as the noncanonical membrane components PA, PE, and PS, were acquired from the medium. Untreated cells (UT) did not fluoresce in the NBD channel. Cells were incubated in dBSK plus 25 μM NBD-labeled phospholipid analogs over a 6-hour period, and then imaged by fluorescence microscopy at ×63 magnification. DAPI stained the nucleic acids nonspecifically. DAPI (Ex = 405 nm, detector = 410–466 nm) and NBD (Ex = 470 nm, detector 550–600 nm) channels were acquired sequentially. Fluorescence intensity (Ex = 465 nm, Em = 540 nm, normalized to OD600) was quantified by fluorimetry. Graphs plot the mean of 3 biological replicates, with error bars indicating the SD. Images are representative of biological triplicate experiments.