Lyme disease has grown from a regional phenomenon to a national epidemic affecting hundreds of thousands of people each year. The current diagnostic standard has several well-recognized limitations that include failure to diagnose Lyme disease early in disease as well as persistently positive test results after previous Lyme disease. Also, tests take 1 to 3 days to return results. These limitations leave clinicians with diagnostic uncertainty and without real-time guidance in the evaluation and treatment of children with potential Lyme disease, leading to delays in selecting and/or initiating appropriate therapy. We propose to identify a novel blood-based biomarker signature to distinguish between patients with Lyme disease and patients with symptoms compatible with Lyme disease but who ultimately were found to have alternate diagnoses; i.e., patients with symptoms mimicking Lyme disease. In pilot studies, we have shown differential abundances of a subset of blood proteins which alone or in combination show promise as a sensitive diagnostic that could be used to improve on currently available diagnostics for early Lyme disease. We hypothesize that a novel blood-based biomarker (or set thereof) has the potential to improve diagnostic accuracy for patients with suspected Lyme disease.

Our effort, which is responsive to the Fiscal Year 2020 Tick-Borne Disease Research Program, will leverage Pedi Lyme Net. Pedi Lyme Net was established by the Principal Investigator, Dr. Nigrovic as a research network of 10 clinical centers, which has enrolled to date more than 2,500 children and adults undergoing evaluation for Lyme disease. Our proposal will use serum samples from previously and newly enrolled patients. First, using serum samples from children with Lyme and non-Lyme arthritis for which the diagnostic standard is well-established, we will use unbiased proteomics to identify serum proteins that distinguish children with Lyme arthritis from its clinical mimics. We will determine how well this proteomics signature performs in an independent cohort of children and adults with arthritis. Second, will refine a proteomic blood-based biomarker signature for children with potential early-disseminated Lyme disease, with the potential to improve on the currently available suboptimal Lyme diagnosis. To ensure statistically sound results, all discovery and validation experiments will be carried out using 100 or more Lyme patients and three times as many controls/mimics.

In summary, we plan to derive and validate a novel Lyme proteomic biosignature for early-disseminated and late Lyme disease with the ultimate goal to enable the timely and reliable diagnosis of Lyme disease to rapidly target appropriate therapies to patients with confirmed disease. Our work will inform the future development of a point-of-care test that could transform our approach to diagnosing Lyme disease with potential for substantial impact on patient care and quality of life for military Service members as well as the American public.