Immunology of Post-Treatment Lyme Disease Syndrome

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.