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
葡萄膜炎是获得性失明的主要原因之一。葡萄膜炎可以根据解剖结构进行细分
受影响的葡萄膜部分; 85%的葡萄膜炎主要是前部。由于HLA B27与
在50%的急性前葡萄膜炎患者中,HLA-B27相关的急性前葡萄膜炎容易发生。
最常见的葡萄膜炎表型。尽管HLA-B7在导致糖尿病的发病机制中发挥着重要作用,
葡萄膜炎,解释这种效果的机制是未知的。使用大鼠模型,我们最近报道,
HLA B27塑造了微生物组,即共同居住在人体内的微生物细胞。此外,我们注意到,
在大鼠模型中用伊加包被特定的肠道细菌,包括关节炎链球菌。此外,本发明还提供了一种方法,
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
通过对患者的观察,显示HLA B27塑造了人体内的微生物组,
细菌在B27+受试者中相对于对照更普遍。我们假设微生物组
与B27相关急性前葡萄膜炎有因果关系。我们进一步假设肠道细菌是
转移到炎症部位如葡萄膜。我们提出3个目的来检验这些假设。这些
研究代表了一种创新的方法来了解HLA B27相关疾病的发病机制,
尽管该协会实力雄厚,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