Auto-antibodies as predictive markers for Post treatment Lyme Disease Syndrome
自身抗体作为治疗后莱姆病综合征的预测标记
基本信息
- 批准号:10737996
- 负责人:
- 金额:$ 55.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-05 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:AffinityAftercareAnimal ModelAnimalsAntibiotic TherapyAntibodiesAnticardiolipin AntibodiesAntigen-Antibody ComplexAntigensAntiphospholipid AntibodiesAreaArthralgiaAutoantibodiesAutoimmuneAutoimmune DiseasesAutoimmune ProcessAutoimmunityBacteriaBacterial ProteinsBindingBorrelia burgdorferiCardiolipinsCellsCommunicable DiseasesComplement ActivationDefectDepositionDevelopmentDiagnostic testsDiseaseElementsEnvironmentFatigueFibromyalgiaGenerationsGenomeHumanHypersensitivityImmune responseImmune systemImmunoglobulin GImmunologic StimulationInfectionInjectionsLaboratoriesLinkLipidsLocomotionLong COVIDLyme DiseaseMacrophageMembraneMemory B-LymphocyteMemory LossMetabolicModelingMusMyalgiaNerve BlockNeurologicNeuronsNutrientOrganismPainPathogenesisPathogenicityPatientsPersonsPhospholipidsPlasminPost Treatment Lyme Disease SyndromeProcessProductionReaginsReceptor ActivationResidual stateResolutionRoleSerumSignal TransductionSymptomsSynaptic TransmissionSyphilisTestingTheftTimeTissuesacute infectionautoreactivitybehavioral studybiomarker identificationbrain tissuecell injurycostcross reactivityderepressionfibromyalgia patientshistological studieslyme pathogenesisneuralpathogenic autoantibodiespatient subsetspersistent symptompredictive markerresponsetreatment response
项目摘要
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.
摘要
作为一种在其天然宿主中持续很长时间的生物体,伯氏疏螺旋体,其致病菌是
莱姆病的病原体,已经适应了许多生存和逃避宿主免疫反应的策略。它
它的基因组非常小,无法为自己生产许多必需的营养素,
从环境中利用它们。我们最近证明了B。burgdorferi能够获得主机
磷脂并将其完整地部署在其膜中。利用宿主磷脂的成本是它可能
导致针对宿主磷脂靶标的自身抗体的产生或去抑制。事实上,在我们的初步
研究中,我们发现小鼠和人类感染了B。伯氏螺旋体产生抗宿主磷脂抗体
生物体本身不会产生的物质。抗磷脂抗体比抗B抗体产生得更快。
burgdorferi和也似乎更快地解决,因为可以预期的是,自身抗体的产生,
通常受到严格监管。然而,与PTLDS患者相比,
在莱姆病治疗后的症状中,抗磷脂抗体水平似乎增加。是
目前尚不清楚这些抗体是致病性的还是仅仅是PTLDS的标志物。
在本提案中,我们将探讨莱姆病期间抗脂质/磷脂抗体的发展,
在PTLDS中的潜在作用。在目标1中,我们将确定抗脂质/磷脂开发的程度,
疾病的不同阶段,并确定它们与疾病消退/持续症状的关系,
莱姆病患者在目标2中,我们将检查这些抗体与人体细胞和组织的结合
并寻找免疫复合物的存在,这些免疫复合物通常沉积在自身免疫性疾病中。最后,
在目标3中,我们将探索一种新的PTLDS动物模型。最近的一项研究表明注射抗体
从纤维肌痛患者(一种在症状上与PTLDS有显著相似性的疾病)到小鼠中,
对疼痛和寒冷的超敏反应以及运动的变化。组织学研究表明,
抗神经组织和巨噬细胞的人类抗体。我们将测试一个类似的模型,
PTLDS患者,莱姆病和纤维肌痛恢复。在初步研究中,我们发现
与来自PTLDS患者的结合相比,来自PTLDS患者的抗体与小鼠脑组织的结合增加
健康对照抗体。抗脂质/磷脂自身抗体的发现为抗脂质/磷脂自身抗体的研究开辟了新的领域。
发现莱姆病的发病机制,并可能导致更好的诊断测试和一个新的
了解这种疾病的发病机制。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Linden T Hu其他文献
Case 24-2015
案例24-2015
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
Linden T Hu;Athe M. N. Tsibris;John A. Branda - 通讯作者:
John A. Branda
Linden T Hu的其他文献
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{{ truncateString('Linden T Hu', 18)}}的其他基金
Laboratory for Combinatorial Drug Regimen Design for Resistant and Emerging Pathogens
耐药和新发病原体组合药物方案设计实验室
- 批准号:
10596722 - 财政年份:2022
- 资助金额:
$ 55.52万 - 项目类别:
Role of human innate immune mutations in loss of tolerance to Borrelia burgdorferi
人类先天免疫突变在伯氏疏螺旋体耐受性丧失中的作用
- 批准号:
10461854 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Development and Field Testing of a Novel Reservoir Targeted Antibiotic Against Borrelia burgdorferi
新型水库靶向伯氏疏螺旋体抗生素的开发和现场测试
- 批准号:
10397615 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Role of human innate immune mutations in loss of tolerance to Borrelia burgdorferi
人类先天免疫突变在伯氏疏螺旋体耐受性丧失中的作用
- 批准号:
10680556 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Development and Field Testing of a Novel Reservoir Targeted Antibiotic Against Borrelia burgdorferi
新型水库靶向伯氏疏螺旋体抗生素的开发和现场测试
- 批准号:
10606624 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Development and Field Testing of a Novel Reservoir Targeted Antibiotic Against Borrelia burgdorferi
新型水库靶向伯氏疏螺旋体抗生素的开发和现场测试
- 批准号:
10165497 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Role of human innate immune mutations in loss of tolerance to Borrelia burgdorferi
人类先天免疫突变在伯氏疏螺旋体耐受性丧失中的作用
- 批准号:
10256713 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Development and Field Testing of a Novel Reservoir Targeted Antibiotic Against Borrelia burgdorferi
新型水库靶向伯氏疏螺旋体抗生素的开发和现场测试
- 批准号:
10674121 - 财政年份:2020
- 资助金额:
$ 55.52万 - 项目类别:
Understanding Human Immunological Responses to Ixodes Tick Bites
了解人类对硬蜱叮咬的免疫反应
- 批准号:
9807836 - 财政年份:2019
- 资助金额:
$ 55.52万 - 项目类别:
Coping with Stress: Next Generation Approaches to Borrelia burgdorferi Host Adaptation
应对压力:伯氏疏螺旋体宿主适应的下一代方法
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9892949 - 财政年份:2017
- 资助金额:
$ 55.52万 - 项目类别:
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