# Immunology of Post-Treatment Lyme Disease Syndrome

> **NIH NIH P01** · TUFTS UNIVERSITY BOSTON · 2024 · $413,308

## Abstract

ABSTRACT: Project 2, Immunology of Post-treatment Lyme Disease Syndrome
Similarities between symptoms of Post-Treatment Lyme Disease Syndrome (PTLDS) and symptoms seen with
fibromyalgia, auto-immune diseases and post-acute sequelae of other infectious diseases are suggestive of a
shared common pathway underlying the symptoms. Immune responses to different stimuli may activate similar
pathways and have long been suspected as a culprit in these syndromes. Prior studies of patients with PTLDS
have shown evidence of specific immune activation when compared with subjects that have recovered from
Lyme disease-- although these studies have been inconsistent between different studies. Multiple auto-
antibodies have been identified after infection with Lyme disease however the association for any specific auto-
antibody remains undetermined. Antibodies from patients with PTLDS vs recovered Lyme disease have been
shown by one group to bind to neural tissue suggesting a possible mechanism for the persistence of
symptoms.
In this Project, we will utilize samples collected by our Clinical Coordination Core to compare responses
between patients with PTLDS and recovered Lyme disease. In Aim 1, we will look at inflammatory responses
to infection both acutely and with persistence of symptoms using multiple unbiased high throughput methods
for examining both protein and gene expression. We will compare the cellular composition between these
groups of patients using high dimensional flow cytometry followed by bulk RNAseq to determine gene
expression within specific cell types. In Aim 2 we will look for correlation of antibodies that recognize either
specific Borrelia burgdorferi components or self-antigens with PTLDS using unbiased Phage display
Immunoprecipitation sequencing technology (PhIPseq) and peptide microarrays. We will also test for the
presence of antibodies to host phospholipids which we have previously identified as potentially linked to
PTLDS. Finally, we will confirm whether antibodies from PTLDS patients preferentially bind neural tissue
compared with serum from recovered Lyme patients. Finally, in Aim 3, we will determine the role of T cell
reactivity in PTLDS. We will look at specific HLA-DR correlations with PTLDS. We will then identify candidate
B. burgdorferi or self-peptides that are presented in association with HLA-DR molecules using nano-liquid
chromatography, tandem mass spectrometry.
At the completion of this Project, we will have tested multiple hypotheses regarding the role of the immune
response to B. burgdorferi in the development of PTLDS. This information will be combined with data from
Projects 1 and 3 to create a multi-modal model of PTLDS development.

## Key facts

- **NIH application ID:** 10862292
- **Project number:** 1P01AI181934-01
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Linden T Hu
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $413,308
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862292

## Citation

> US National Institutes of Health, RePORTER application 10862292, Immunology of Post-Treatment Lyme Disease Syndrome (1P01AI181934-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862292. Licensed CC0.

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