Lyme disease is a multisystem illness caused by infection with the spirochete Borrelia burgdorferi and it is the leading vector-borne disease in the United States. Our current work addresses the following areas in Lyme disease: development of new tests and biomarkers for infection, investigation of persistence of infection with B. burgdorferi in humans, and investigation of the role of immune response in Lyme disease and post treatment Lyme disease syndrome (PTLDS). One of the main problems in Lyme diagnosis has been the lack of highly specific and sensitive assays for B. burgdorferi and the lack of a test that could be used to assess response to therapy. Such assays should greatly facilitate the accurate diagnosis of Lyme disease and assessment of response to therapy in individual patients. Currently, no such test is available. We have developed a test using the luciferase immunoprecipitation systems (LIPSs) for profiling of the antibody responses to a panel of B. burgdorferi proteins for the diagnosis of Lyme disease. The test displays a wide dynamic range of antibody detection and offers an efficient quantitative approach for evaluation of the antibody responses in patients with Lyme disease. Recent studies have shown that B. burgdorferi may persist in animals after antibiotic therapy and can be detected by using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding. Whether this occurs in humans is unknown. We have completed a phase I study to investigate the utility of this approach for identifying persistence of B. burgdorferi in treated human Lyme disease. Inflammatory innate immune responses are critical in the control of early disseminated infection, while adaptive immune responses are vitally important, particularly the humoral immune response, in controlling spirochete levels in tissues and resolution of Lyme arthritis in animal models. We are examining the antibody response to immunogenically dominant antigens of B. burgdorferi in PTLDS patients and controls. Further investigation of the anti-borrelia immune response may help in elucidating the pathogenic mechanism of PTLDS and yield important information for future approaches to diagnosis and treatment. We have a clinical protocol in which we use microarrays to characterize gene expression patterns in skin biopsies from individuals with EM, with the aim of capturing the human host response to pathogen exposure. We are also investigating the immunological response in neuroborreliosis. Results from these studies will serve as a window into the fundamental biology of the infection.

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20
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2015
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Branda, John A; Body, Barbara A; Boyle, Jeff et al. (2018) Advances in Serodiagnostic Testing for Lyme Disease Are at Hand. Clin Infect Dis 66:1133-1139
Uhde, Melanie; Indart, Alyssa; Fallon, Brian A et al. (2018) C-Reactive Protein Response in Patients With Post-Treatment Lyme Disease Symptoms Versus Those With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clin Infect Dis 67:1309-1310
Marques, Adriana R (2018) Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers. J Clin Microbiol 56:
Tokarz, Rafal; Mishra, Nischay; Tagliafierro, Teresa et al. (2018) A multiplex serologic platform for diagnosis of tick-borne diseases. Sci Rep 8:3158
Turk, Siu-Ping; Williams, Carla; Marques, Adriana (2018) Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans. Methods Mol Biol 1690:337-346
Bernard, Quentin; Smith, Alexis A; Yang, Xiuli et al. (2018) Plasticity in early immune evasion strategies of a bacterial pathogen. Proc Natl Acad Sci U S A 115:E3788-E3797
Uhde, Melanie; Ajamian, Mary; Wormser, Gary P et al. (2017) Reply to Naktin. Clin Infect Dis 64:1145-1146
Pavletic, Adriana J; Marques, Adriana R (2017) Early Disseminated Lyme Disease Causing False Positive Serology for Primary Epstein-Barr Virus Infection - Report of 2 Cases. Clin Infect Dis :
Marques, Adriana R; Yang, Xiuli; Smith, Alexis A et al. (2017) Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol 55:3297-3299
Marques, Adriana; Schwartz, Ira; Wormser, Gary P et al. (2017) Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling. J Infect Dis 217:158-167

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