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
伯氏疏螺旋体作为一种长期存在于其自然宿主中的生物体,其病原菌
莱姆病的代理人,已经采取了许多策略来生存和逃避宿主的免疫反应。它
基因组非常小,不能为自己产生许多必要的营养物质,相反,依赖于
从它的环境中利用它们。我们最近发现伯氏杆菌能够获得宿主
磷脂,并将它们完整地部署在其膜中。利用宿主磷脂的成本是它可以
导致产生或抑制针对宿主磷脂靶标的自身抗体。事实上,在我们的初选中
研究发现,感染伯氏杆菌的小鼠和人类会产生针对宿主磷脂的抗体。
生物体本身不会产生。抗磷脂抗体比其他抗B组抗体出现得快。
Burgdorferi和似乎也更快地解决,正如可能预期的那样,因为自身抗体的产生
通常受到严格的监管。然而,在PTLDS患者中,与解决其症状的患者相比
症状治疗莱姆病后,抗磷脂抗体水平似乎有所上升。它是
目前尚不清楚这些抗体可能是致病的,还是只是PTLDS的一个标志。
在这项建议中,我们将探讨抗脂/磷脂抗体在莱姆病和
它们在PTLDS中的潜在作用。在目标1中,我们将确定抗脂/磷脂的发展程度
疾病的不同阶段,并确定它们与疾病解决/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类细胞和组织的结合。
并寻找免疫复合体的存在,这些免疫复合体通常在自身免疫性疾病中沉积。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有显著相似之处的疾病,进入老鼠体内,结果是
对疼痛和寒冷以及运动能力的改变过敏。组织学研究表明,
人类对神经组织和巨噬细胞的抗体。我们将测试一个类似的模型,使用来自
PTLDS患者恢复莱姆病和纤维肌痛。在我们的初步研究中,我们发现
PTLDS患者的抗体与小鼠脑组织的结合比来自PTLDS患者的抗体更强
健康对照抗体。抗脂/磷脂自身抗体的发现开辟了一个新的领域
莱姆病发病机制的发现,并可能导致更好的诊断试验和新的
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
- 批准号:
9892949 - 财政年份:2017
- 资助金额:
$ 55.52万 - 项目类别:
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