Generation of IgG and IgE autoantibodies in an active mouse model of Bullous pemphigoid
在大疱性类天疱疮活跃小鼠模型中产生 IgG 和 IgE 自身抗体
基本信息
- 批准号:10428671
- 负责人:
- 金额:$ 7.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-14 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsAddressAdhesionsAffectAnimal Disease ModelsAntibodiesAntigensAutoantibodiesAutoantigensAutoimmuneAutoimmune DiseasesAutoimmunityBP180 autoantigenBasement membraneBindingBiopsyBullaBullous PemphigoidCellsCollagen Type XVIICutaneousDataDepositionDevelopmentDiseaseDisease ProgressionDisease modelDoseElderlyEventFormalinFutureGenerationsGoalsHealthHomologous GeneHumanIgEIgG autoantibodiesImmuneImmunizationImmunizeImmunoglobulin GImmunologicsImmunosuppressionInflammationInjectionsIntranasal AdministrationInvestigationKnowledgeLeadLesionLifeMediatingMissionModelingMolecularMorbidity - disease rateMusNational Institute of Allergy and Infectious DiseaseNatureOnset of illnessParaffin EmbeddingPassive Transfer of ImmunityPathogenesisPathogenicityPatientsPlayPopulationPreventionProtein IsoformsProteinsRecombinantsRegimenResearchRoleRouteSJL/J MouseSamplingSecondary ImmunizationSkinStudy modelsTestingTissuesTranslatingUnited States National Institutes of Healthcellular targetingeffective therapyhuman diseasehuman modelhuman subjectimmune activationimprovedimproved outcomein vivoinnovationinsightmortalitymouse modelperipheral toleranceresponseskin disorderstandard caretargeted treatmenttherapy outcometool
项目摘要
PROJECT SUMMARY
There is a fundamental gap in our understanding of the pathogenic mechanisms of Bullous pemphigoid (BP), an
autoimmune blistering disease. Thus, standard treatment consists of high dose immunosuppression, which is
associated with significant morbidity and mortality in the elderly population typically affected by BP. Our long-
term goal is to identify the cellular and molecular events that lead to the development and propagation of
cutaneous autoimmunity so that better therapies can be developed. The objective of this proposal is to develop
an active mouse model of BP that recapitulates human disease by eliciting both IgE and IgG autoantibodies BP.
Although BP is one of a growing number of autoimmune diseases characterized by pathogenic IgE
autoantibodies, and these IgE antibodies are critical for recapitulation of human disease in passive transfer
models of disease, there is no active disease model that includes both an IgG and an IgE response to the BP
autoantigen. Our hypothesis that the route of antigen exposure is critical for the development of an IgE
autoantibody response. The rationale for the proposed research is generation of a robust active model of BP will
address the shortcomings of current passive models and will facilitate studies of the basic mechanisms of BP
and other instances of IgE-mediated autoimmunity. Guided by our preliminary data, this hypothesis will be tested
by pursuing the following specific aim: To identify the immunization regimen that generates mBP180-specific IgE
and IgG and cutaneous lesions consistent with BP. Mice will be immunized with the murine homolog of the BP
autoantigen to determined how the route of antigen exposure influences the form and nature of the autoantibody
response. At regular intervals, the extent of skin disease, the level of circulating antibodies, and the cutaneous
immune cell populations will be assessed. These studies are relevant to the NIH’s mission aimed at enhancing
health, lengthening life and reducing illness, and to that of the NIAID to better understand the immunologic basis
of disease, including developing a greater understanding of fundamental immunologic principles underlying
disease onset and progression and developing improved animal models of disease. This approach is innovative
because there are currently no established mouse models of human autoimmune diseases that feature IgE. The
proposed studies are significant because they will advance and expand our understanding of the basic
mechanisms of cutaneous autoimmunity and will lay the groundwork for future studies aimed at identifying the
cellular and molecular mechanisms of disease that can be targeted therapeutically.
项目总结
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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Kelly A.N. Messingham其他文献
Autoantibodies to Collagen XVII Are Present in Parkinson’s Disease and Localize to Tyrosine-Hydroxylase Positive Neurons
- DOI:
10.1016/j.jid.2015.12.005 - 发表时间:
2016-03-01 - 期刊:
- 影响因子:
- 作者:
Kelly A.N. Messingham;Samantha Aust;Joseph Helfenberger;Krystal L. Parker;Susan Schultz;Julie McKillip;Nandakumar S. Narayanan;Janet A. Fairley - 通讯作者:
Janet A. Fairley
Role of gonadal hormones after alcohol and burn injury
- DOI:
10.1016/j.alcohol.2006.09.019 - 发表时间:
2006-06-01 - 期刊:
- 影响因子:
- 作者:
John Karavitis;Douglas E. Faunce;Luis Ramirez;Kelly A.N. Messingham;Elizabeth J. Kovacs - 通讯作者:
Elizabeth J. Kovacs
Kelly A.N. Messingham的其他文献
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{{ truncateString('Kelly A.N. Messingham', 18)}}的其他基金
Generation of IgG and IgE autoantibodies in an active mouse model of Bullous pemphigoid
在大疱性类天疱疮活跃小鼠模型中产生 IgG 和 IgE 自身抗体
- 批准号:
10283432 - 财政年份:2021
- 资助金额:
$ 7.73万 - 项目类别:
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