HLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUS
HLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUS
批准号:
3137908
负责人:
Courtney Montgomery
金额:
$12.52万
依托单位国家:
美国
项目类别:
财政年份:
1987
资助国家:
美国
项目状态:
已结题
起止时间:
1987-04-01 至 1990-03-31
中文摘要
自身免疫性疾病中自身抗体的产生与特定的
在主要组织相容性复合体中发现的等位基因或单倍型。 我们
实验室已经证明了HLA-DQ的基因相互作用的强烈效果。
抗Ro/SSA、抗La/AAB和类风湿因子自身抗体的产生
在原发性干燥综合征中,以及在系统性狼疮中抗Ro/SSA
在HLA-DQ杂合子患者中,
等位基因DQ 1和DQ 2。 由于HLA-DQ表面分子由两个
肽(α和β),并且由于这两种肽都是多态的,
可产生反式相关的表面分子,其具有独特的抗原性,
特殊性 这些分子的存在以前一直是
证明,但没有特异性的免疫反应,
我们将检验自身抗体
原发性干燥综合征和系统性狼疮中抗Ro/SSA的产生
红斑狼疮是由于HLA-DQ的基因互补而增强的。
我们建议直接鉴定相关基因。 基因探针
单独的肽,DQAlpha、DQBeta和DRAlpha将杂交到
来自患者的限制性酶消化和Southern印迹的基因组DNA
原发性干燥综合征系统性红斑狼疮和正常人
将对这些患者的家系进行分析,
限制性片段长度多态性和HLA的命名
血清学 可能的模型(特别是基因互补)将是
测试他们的能力,以解释从
自身抗体血清学、HLA数据和限制性片段长度
多态性分型分析 即使这一分析确定了一个主要的
由于基因互补的作用,可能会有一些患者
其数据不符合明显的主效应。 的解释
将使用其它试剂来寻找主要效应的例外。
单克隆抗体、HLA反应性T细胞系和基因探针将被用于
提出并用于确定关键结构的贡献
组件,以确定它们是否在功能上类似于
解释了主要效应(现在在DQ 1/DQ 2杂合子中发现)。
这些额外的试剂将被用于绘制这些影响,
主要组织相容性复合体 对于精心选择的实例,
基因的可变区将被测序,
可能是寻找分子结构中重要的相似性。 这
这项研究将使我们更接近自身免疫性疾病的机制,
阐明影响诱导的遗传因素和/或
原发性干燥综合征和全身性干燥综合征中自身抗体的产生
红斑狼疮 所产生的试剂可能有望改善
诊断,也许,治疗。
英文摘要
Autoantibody production in autoimmune diseases is related to particular
alleles or haplotypes found in the major histocompatibility complex. Our
laboratory has demonstrated a strong effect of gene interaction of HLA-DQ.
Autoantibody production of anti-Ro/SSA, anti-La/AAB and rheumatoid factor
in primary Sjogren's syndrome, and of anti-Ro/SSA in systemic lupus
erythematosus is dramatically higher in patients heterozygous at HLA-DQ for
alleles DQ1 and DQ2. Since the HLA-DQ surface molecule is composed of two
peptides (Alpha and Beta) and since both of these peptides are polymorphic,
trans-associated surface molecules may result which have unique antigenic
specificities. The existence of these molecules has been previously
demonstrated, but no immune reactivity specific for them has been
previously known in man. We will test the hypothesis that autoantibody
production in primary Sjorgren's syndrome and anti-Ro/SSA in systemic lupus
erythematosus are enhanced as a result of gene complementation at HLA-DQ.
We propose to directly identify the genes involved. Gene probes for the
individual peptides, DQAlpha, DQBeta and DRAlpha will be hybridized to the
restriction enzyme digested and Southern blotted genomic DNA from patients
with primary Sjogren's syndrome, systemic lupus erythematosus and normals.
Pedigrees from these patients will be analyzed to make haplotype
designation of the restriction fragment length polymorphisms and of HLA
serology. The possible models (especially gene complementation) will be
tested for their capacity to explain the combined data obtained from
autoantibody serology, the HLA data and restriction fragment length
polymorphism typing analysis. Even if this analysis identifies a major
effect from gene complementation, there will likely be a number of patients
whose data does not fit the apparent main effect. Explanations for the
exceptions to the major effects will be sought using other reagents.
Monoclonal antibodies, HLA responsive T cell lines and gene probes will be
raised and used to identify the critical structures of the contributing
components to determine whether they are functionally similar to those
accounting for the major effect (now found in DQ1/DQ2 heterozygotes).
These additional reagents will be used to map these effects within the
major histocompatibility complex. For carefully selected instances, the
variable regions of the genes in question will be sequenced to make
possible a search for important similarities in molecular structure. This
study will bring us closer to the mechanism of autoimmune disease by
elucidating the genetic elements which influence induction and/or
production of autoantibodies in primary Sjogren's syndrome and systemic
lupus erythematosus. Reagents generated may hold promise for improved
diagnosis and, perhaps, therapy.
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Quantitative Analysis Core
-
批准号:8751104
-
项目类别:
-
资助金额:$40.06万
-
财政年份:2014
-
负责人:Courtney Montgomery
-
依托单位:
Comprehensive Genome Interrogation of African American Sarcoidosis Families
-
批准号:8451530
-
项目类别:
-
资助金额:$109.55万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
Comprehensive Genome Interrogation of African American Sarcoidosis Families
-
批准号:9120477
-
项目类别:
-
资助金额:$111.32万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
Comprehensive Genome Interrogation of African American Sarcoidosis Families
-
批准号:8645728
-
项目类别:
-
资助金额:$117.96万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
Comprehensive Genome Interrogation of African American Sarcoidosis Families
-
批准号:8823655
-
项目类别:
-
资助金额:$80.54万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
Comprehensive Genome Interrogation of African American Sarcoidosis Families
-
批准号:9041664
-
项目类别:
-
资助金额:$80.83万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
Characterization of European American and African American Sarcoidosis via Immunogenetics
-
批准号:10376788
-
项目类别:
-
资助金额:$77.52万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
Comprehensive Genome Interrogation of African American Sarcoidosis Families
-
批准号:8283045
-
项目类别:
-
资助金额:$57.83万
-
财政年份:2012
-
负责人:Courtney Montgomery
-
依托单位:
GENES FOR EARLY SYSTEMIC LUPUS ERYTHEMATOSUS AUTOIMMUNITY
-
批准号:8359794
-
项目类别:
-
资助金额:$15.51万
-
财政年份:2011
-
负责人:Courtney Montgomery
-
依托单位:
GENETICS OF EARLY LUPUS AUTOIMMUNITY IN AFRICAN AMERICANS
-
批准号:8168262
-
项目类别:
-
资助金额:$16.29万
-
财政年份:2010
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC DISSECTION OF INSULIN RESISTANCE IN CANCER AND METABOLIC FUNCTION
-
批准号:7956485
-
项目类别:
-
资助金额:$0.48万
-
财政年份:2009
-
负责人:Courtney Montgomery
-
依托单位:
African American Sarcoidosis Genetics Resource
-
批准号:7940825
-
项目类别:
-
资助金额:$30.0万
-
财政年份:2009
-
负责人:Courtney Montgomery
-
依托单位:
African American Sarcoidosis Genetics Resource
-
批准号:7854835
-
项目类别:
-
资助金额:$170.0万
-
财政年份:2009
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC LINKAGE IN LUPUS
-
批准号:7723435
-
项目类别:
-
资助金额:$0.46万
-
财政年份:2008
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC DISSECTION OF INSULIN RESISTANCE IN CANCER AND METABOLIC FUNCTION
-
批准号:7723450
-
项目类别:
-
资助金额:$0.45万
-
财政年份:2008
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC DISSECTION OF INSULIN RESISTANCE IN CANCER AND METABOLIC FUNCTION
-
批准号:7601000
-
项目类别:
-
资助金额:$0.51万
-
财政年份:2007
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC LINKAGE IN LUPUS
-
批准号:7600972
-
项目类别:
-
资助金额:$0.51万
-
财政年份:2007
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC LINKAGE IN LUPUS
-
批准号:7420620
-
项目类别:
-
资助金额:$0.74万
-
财政年份:2006
-
负责人:Courtney Montgomery
-
依托单位:
GENETIC LINKAGE IN LUPUS
-
批准号:7181269
-
项目类别:
-
资助金额:$0.44万
-
财政年份:2005
-
负责人:Courtney Montgomery
-
依托单位:
PEPTIDES INDUCE LUPUS AUTOIMMUNITY
-
批准号:2081761
-
项目类别:
-
资助金额:$4.92万
-
财政年份:1995
-
负责人:Courtney Montgomery
-
依托单位:
海外基金