The Gut Microbiome and HLA B27-associated Acute Anterior Uveitis
The Gut Microbiome and HLA B27-associated Acute Anterior Uveitis
批准号:
10228030
负责人:
JAMES T ROSENBAUM
金额:
$36.33万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-01 至 2022-05-31
关键词:
16S ribosomal RNA sequencingAcquired BlindnessAcuteAdultAffectAnatomyAnkylosing spondylitisAnteriorAnterior uveitisAntigensBacteriaBiopsyBlindnessBloodCell surfaceCellsClinicalColitisColonoscopyCommunitiesComplementComplexDegenerative polyarthritisDepositionDiseaseEcosystemElementsFOXP3 geneFecesFrequenciesGene ExpressionGoalsHLA-B27 AntigenHabitsHouseholdHumanHuman MicrobiomeHuman bodyImmuneImmunoglobulin AImmunologicsIndividualInflammationInflammation MediatorsInflammatoryInterleukin-17IntestinesJointsLCN2 geneLengthLeukocyte L1 Antigen ComplexLeukocytesLymphoid CellMajor Histocompatibility ComplexMediatingMicrobeModelingMucosal Immune SystemOrganismPathogenesisPathogenicityPathologyPatientsPhenotypePlayPopulationPsoriatic ArthritisRattusRecording of previous eventsRegulatory T-LymphocyteReiter DiseaseReportingRheumatoid ArthritisRiskRoleSamplingShapesSiteSpondylarthritisSynovial MembraneSynovitisTestingTransgenic OrganismsUveaUveitisViralarthropathiesbasefecal microbiomegut bacteriagut microbesgut microbiomehuman diseaseinnovationmicrobialmicrobiomemicrobiotamouse modelnext generation sequencingnovelpreventrRNA Genestranscriptome sequencing
中文摘要
项目摘要
葡萄膜炎是后天致盲的主要原因之一。葡萄膜炎可根据解剖学进行细分
葡萄膜受影响的部分;85%的葡萄膜炎主要发生在前部。由于人类白细胞抗原B27与
在50%发生急性前葡萄膜炎的患者中,HLAB27相关的急性前葡萄膜炎很容易
葡萄膜炎最常见的表型。尽管人类白细胞抗原B7在S的发病机制中起到了显著作用
葡萄膜炎,解释这种影响的机制尚不清楚。使用老鼠模型,我们最近报告了
人类白细胞抗原B27塑造了微生物群,即共同栖息在人体内的微生物细胞。此外,我们注意到,
在大鼠模型中,特定的肠道细菌,包括关节假丝酵母菌,被IgA包被。此外,
大鼠模型中的细菌从肠道转移到关节。重要的是,我们已经推断出这些
人类白细胞抗原B27塑造人体微生物群并包被免疫球蛋白对患者的观察
与对照组相比,细菌在B27+受试者中更普遍。我们假设微生物群是
与B27相关的急性前葡萄膜炎有因果关系。我们进一步假设肠道细菌是
转移到葡萄膜等发炎部位。我们提出3个目标来检验这些假说。这些
研究代表了一种理解HLAB27相关疾病发病机制的创新方法,这是一个目标
尽管该协会很强大,但43年来一直难以捉摸。
英文摘要
Project Summary
Uveitis is one of the leading causes of acquired blindness. Uveitis can be subdivided based on the anatomic
portion of the uvea that is affected; 85% of uveitis is predominantly anterior. Since HLA B27 is associated with
50% of the patients who develop acute anterior uveitis, HLA B27 related acute anterior uveitis is easily the
most common phenotype of uveitis. Despite HLA B7’s remarkable role in contributing to the pathogenesis of
uveitis, the mechanism that explains this effect is unknown. Using a rat model, we have recently reported that
HLA B27 shapes the microbiome, the microbial cells that co-habit the human body. Furthermore, we note that
specific gut bacteria including Candidatus arthromatus are coated with IgA in the rat model. In addition,
bacteria in the rat model are translocated from the gut to the joint. Importantly we have extrapolated these
observations to patients by showing that HLA B27 shapes the microbiome in people and that IgA coated
bacteria are more prevalent in B27+ subjects relative to controls. We hypothesize that the microbiome is
causally related to B27-related acute anterior uveitis. We further hypothesize that intestinal bacteria are
translocated to sites of inflammation such as the uvea. We propose 3 aims to test these hypotheses. These
studies represent an innovative approach to understand the pathogenesis of HLA B27-related disease, a goal
which has been elusive for 43 years despite the strength of the association.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1038/s41598-020-74751-0
发表时间:
2020-10-19
期刊:
Scientific reports
影响因子:
4.6
作者:
[Sternes PR, Martin TM, Paley M, Diamond S, Asquith MJ, Brown MA, Rosenbaum JT]
通讯作者:
Rosenbaum JT
DOI:
10.1002/art.41018
发表时间:
2019-11
期刊:
Arthritis & rheumatology (Hoboken, N.J.)
影响因子:
--
作者:
[Gill T, Brooks SR, Rosenbaum JT, Asquith M, Colbert RA]
通讯作者:
Colbert RA
Characterizing Uveitis by Gene Expression
-
批准号:9235011
-
项目类别:
-
资助金额:$38.5万
-
财政年份:2017
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:8547813
-
项目类别:
-
资助金额:$41.55万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Understanding uveitis in a multi-system disease model of spondyloarthropathy
-
批准号:8153482
-
项目类别:
-
资助金额:$38.5万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:8206876
-
项目类别:
-
资助金额:$43.74万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Understanding uveitis in a multi-system disease model of spondyloarthropathy
-
批准号:8328922
-
项目类别:
-
资助金额:$38.5万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:8726404
-
项目类别:
-
资助金额:$42.87万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:10016308
-
项目类别:
-
资助金额:$64.94万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:8328921
-
项目类别:
-
资助金额:$43.74万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Understanding uveitis in a multi-system disease model of spondyloarthropathy
-
批准号:8534131
-
项目类别:
-
资助金额:$36.58万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:9769746
-
项目类别:
-
资助金额:$64.94万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Gene Expression in Nonspecific Orbital Inflammatory Disease
-
批准号:9174345
-
项目类别:
-
资助金额:$65.25万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Understanding uveitis in a multi-system disease model of spondyloarthropathy
-
批准号:8726407
-
项目类别:
-
资助金额:$37.73万
-
财政年份:2011
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Endotoxin-induced Uveitis Revisited
-
批准号:7905739
-
项目类别:
-
资助金额:$47.5万
-
财政年份:2009
-
负责人:JAMES T ROSENBAUM
-
依托单位:
Endotoxin-induced Uveitis Revisited
-
批准号:7675158
-
项目类别:
-
资助金额:$46.39万
-
财政年份:2009
-
负责人:JAMES T ROSENBAUM
-
依托单位:
UVEITIS GENE-EXPRESSION PROFILING
-
批准号:7233126
-
项目类别:
-
资助金额:$49.56万
-
财政年份:2005
-
负责人:JAMES T ROSENBAUM
-
依托单位:
UVEITIS GENE-EXPRESSOIN PROFILING
-
批准号:7081281
-
项目类别:
-
资助金额:$48.42万
-
财政年份:2005
-
负责人:JAMES T ROSENBAUM
-
依托单位:
UVEITIS GENE-EXPRESSION PROFILING
-
批准号:6924077
-
项目类别:
-
资助金额:$48.94万
-
财政年份:2005
-
负责人:JAMES T ROSENBAUM
-
依托单位:
"REMICADE" IN THE MANAGEMENT OF VISION-THREATENING UVEITIS
-
批准号:7206566
-
项目类别:
-
资助金额:$4.79万
-
财政年份:2005
-
负责人:JAMES T ROSENBAUM
-
依托单位:
UVEITIS GENE-EXPRESSION PROFILING
-
批准号:7467897
-
项目类别:
-
资助金额:$49.83万
-
财政年份:2005
-
负责人:JAMES T ROSENBAUM
-
依托单位:
"Remicade" in the Management of Vision-Threatening Uveitis
-
批准号:6981089
-
项目类别:
-
资助金额:$3.73万
-
财政年份:2003
-
负责人:JAMES T ROSENBAUM
-
依托单位:
海外基金