Document text
Principal Investigator: Linden T Hu
Organization: TUFTS UNIVERSITY BOSTON
Fiscal Year: 2024
Award: $616,612
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
As an organism that persists in its natural hosts for long periods of time, Borrelia burgdorferi, the causative
agent of Lyme disease, has adapted many strategies for survival and evasion of host immune responses. It
has a very small genome and is unable to produce many essential nutrients for itself and is instead, dependent
upon utilizing them from its environment. We have recently shown that B. burgdorferi is able to acquire host
phospholipids and deploy them, intact, in its membrane. A cost of utilizing host phospholipids is that it may
result in production, or de-repression of autoantibodies to host phospholipid targets. Indeed, in our preliminary
studies, we found that mice and humans infected with B. burgdorferi produce antibodies to host phospholipids
that the organism itself does not produce. Antibodies to phospholipids arise quicker than other antibodies to B.
burgdorferi and also appear to resolve more quickly, as might be expected since autoantibody production is
typically tightly regulated. However, in patients with PTLDS as compared with patients who resolve their
symptoms after treatment for Lyme, there appears to be increased levels of anti-phospholipid antibodies. It is
unknown whether these antibodies may be pathogenic or are just a marker for PTLDS.
In this proposal, we will explore the development of anti-lipid/phospholipid antibodies during Lyme disease and
their potential role in PTLDS. In Aim 1, we will determine the extent of anti-lipid/phospholipid development at
different stages of disease and determine their relationship to disease resolution/persistent symptoms in
patients with Lyme disease. In Aim 2, we will examine binding of these antibodies to human cells and tissues
and look for the presence of immune complexes which are often deposited in auto-immune diseases. Finally,
in Aim 3, we will explore a new animal model for PTLDS. A recent study has shown that injection of antibodies
from patients with fibromyalgia, a disease with marked similarities to PTLDS in symptoms, into mice results in
hypersensitivity to pain and cold as well as changes in locomotion. Histological studies have shown binding of
the human antibodies to neural tissues and macrophages. We will test a similar model using serum from
patients with PTLDS, recovered Lyme disease and fibromyalgia. In our preliminary studies, we have found
increased binding of antibodies from PTLDS patients to mouse brain tissue compared with binding from
healthy control antibodies. The discovery of autoantibodies to lipids/phospholipids opens a new area for
discovery in the pathogenesis for Lyme disease and may lead to better diagnostic tests and a new
understanding of the pathogenesis of this disease.
Terms: <7S Gamma Globulin><Aching muscles><Affinity><After Care><After-Treatment><Aftercare><Allergy><Animal Model><Animal Models and Related Studies><Animals><Antibiotic Therapy><Antibiotic Treatment><Antibodies><Anticardiolipin Antibodies><Antigen-Antibody Complex><Antigens><Antiphospholipid Antibodies><Area><Arthralgia><Autoantibodies><Autoimmune><Autoimmune Diseases><Autoimmune Mechanism><Autoimmune Process><Autoimmune Status><Autoimmunity><B burgdorferi><B. burgdorferi><Bacteria><Bacterial Gene Products><Bacterial Gene Proteins><Bacterial Proteins><Binding><Blood Serum><Body Tissues><Borrelia burgdorferi><Borrelia burgdorferi sensu stricto><Borreliella burgdorferi><Cardiolipins><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cellular injury><Communicable Diseases><Complement Activation><Defect><Deposit><Deposition><Development><Diagnostic tests><Diffuse Myofascial Pain Syndrome><Disease><Disorder><Elements><Environment><Fatigue><Fibrinolysin><Fibromyalgia><Fibromyositis-Fibromyalgia Syndrome><Fibrositis><Generations><Genome><Glu-Plasmin><Human><Hypersensitivity><IgG><Immune Complex><Immune response><Immune system><Immunoglobulin G><Immunologic Stimulation><Immunological Stimulation><Immunological response><Immunostimulation><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Injections><Intracellular Communication and Signaling><Joint Pain><Laboratories><Lack of Energy><Link><Lipids><Locomotion><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Lyme Borreliosis><Lyme Disease><Lyme Disease Spirochete><Lyme disease pathogenesis><MPD syndrome><Macrophage><Membrane><Memory B Cell><Memory B-Lymphocyte><Memory Loss><Metabolic><Mice><Mice Mammals><Modeling><Modern Man><Molecular Interaction><Murine><Mus><Muscle discomfort><Muscle pain><Muscle pain/fibrositis><Muscle sorenesss><Muscular Rheumatism><Myalgia><Myalgic><Myodynia><Myoneuralgia><Myosalgia><Mφ><Nerve Block><Nerve Cells><Nerve Unit><Neural Block><Neural Blockade><Neural Cell><Neural Transmission><Neurocyte><Neurologic><Neurological><Neurons><Nutrient><Organism><Pain><Painful><Pathogenesis><Pathogenicity><Patients><Persons><Phosphatides><Phospholipids><Plasmin><Post Treatment Lyme Disease Syndrome><Process><Production><Protease F><Reagins><Receptor Activation><Residual><Residual state><Resolution><Role><Serum><Signal Transduction><Signal Transduction Systems><Signaling><Stealing><Symptoms><Synaptic Transmission><Syphilis><Testing><Theft><Time><Tissues><acute infection><autoimmune antibody><autoimmune condition><autoimmune disorder><autoimmune reactivity><autoimmunity disease><autoreactive antibody><autoreactivity><bacterial disease treatment><bacterial infectious disease treatment><behavior study><behavioral study><biological signal transduction><biomarker identification><brain tissue><cell damage><cell injury><cellular damage><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><chronic symptom><complement pathway regulation><cost><cross reactivity><damage to cells><derepression><developmental><fibromyalgia patients><fibromyalgia syndrome><great pox><histologic studies><histological studies><host response><identification of biomarkers><identification of new biomarkers><immune system response><immunogen><immunoresponse><injury to cells><living system><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><lyme pathogenesis><lyme spirochete><marker identification><membrane structure><memory decline><model of animal><myofascial pain dysfunction syndrome><neural><neuronal><pathogenic autoantibodies><patient subclass><patient subcluster><patient subgroups><patient subpopulations><patient subsets><patient subtypes><patients with fibromyalgia><persistent COVID-19><persistent symptom><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post treatment><post-acute phases of COVID-19><predictive biomarkers><predictive marker><predictive molecular biomarker><prolonged COVID-19 symptoms><resolutions><response><response to therapy><response to treatment><self reactive antibody><social role><therapeutic response><therapy response><treatment response><treatment responsiveness>