# Determinants of Post-Treatment Phenotypes in Lyme Disease

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $620,364

## Abstract

PROJECT SUMMARY/ABSTRACT
It is unknown why some patients regain their pre-morbid health following appropriate treatment for Lyme disease
while others progress to develop post-treatment Lyme disease (PTLD). Significant prior published and
preliminary data suggest that variability in clinical, immunologic, and metabolic factors at the onset of infection
with B. burgdorferi contribute to the development of divergent post-treatment outcomes, including PTLD. In this
study, we will draw upon unique cohorts of patients with well-defined PTLD, healthy controls without a history of
Lyme disease, and patients with early Lyme disease followed longitudinally up to 1 year after the end of
treatment. Combining advanced, innovative statistical and laboratory methods, the objective of this grant is to
identify these factors and examine how they relate to underlying symptom phenotypes among patients with
PTLD. To accomplish this goal, we will identify clinically-relevant risk factors associated with post-treatment
outcomes in Lyme disease over time. These factors will then be used to develop an assessment score to identify
patients at increased risk of developing PTLD in the clinical setting (AIM 1). A longitudinal, multivariate, cross-
domain analysis of this sort with the goal of direct translation of findings to clinical practice and the study of
fundamental disease pathways in PTLD has not previously been performed. We will also identify novel auto-
antibodies that are associated with PTLD through protein array, and examine their relationship with underlying
clinical phenotypes (AIM 2). While an autoimmune process has been suspected to underlie the pathogenesis of
PTLD, at least for some individuals, adaptive immune recognition of self-antigens is only beginning to be
described. Discovery of autoantibodies in PTLD may reveal patient subsets marked by specific clinical features,
such as predominant musculoskeletal pain or neurologic symptoms, and identify individuals whose disease is
driven by an autoimmune process. Finally, we will study the longitudinal immunometabolic profile of patients with
differing clinical outcomes using a novel, high-dimensional flow cytometry approach, and hypothesize that
pharmacologic manipulation of perturbed pathways in vitro may be able to normalize a PTLD-associated
metabolic signature (AIM 3). The ability of immunometabolism to globally report on the acute cellular
environment suggests that interrogating immune cell metabolism in individuals develop PTLD in the future could
provide fundamental insights into disease mechanism. Collectively, our studies represent a rigorous approach
towards uncovering determinants that are associated with the outcome of PTLD and its underlying clinical
phenotypes. The long-term goal of this project is to generate fundamental knowledge to inform the development
of innovative therapeutic strategies as well as novel interventions to prevent or reduce the often significant
symptom burden and functio...

## Key facts

- **NIH application ID:** 10877114
- **Project number:** 5R01AI178726-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** John Aucott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $620,364
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877114

## Citation

> US National Institutes of Health, RePORTER application 10877114, Determinants of Post-Treatment Phenotypes in Lyme Disease (5R01AI178726-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10877114. Licensed CC0.

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