Shared HLA Class I and II Alleles and Clonally Restricted Public and Private Brain-Infiltrating αβ T Cells in a Cohort of Rasmussen Encephalitis Surgery Patients.
Shared HLA Class I and II Alleles and Clonally Restricted Public and Private Brain-Infiltrating αβ T Cells in a Cohort of Rasmussen Encephalitis Surgery Patients.
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DOI：
10.3389/fimmu.2016.00608
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发表时间：
2016
影响因子：
7.3
通讯作者：
Owens GC
中科院分区：
文献类型：
--
作者：
Dandekar S;Wijesuriya H;Geiger T;Hamm D;Mathern GW;Owens GC
Rasmussen encephalitis (RE) is a rare pediatric neuroinflammatory disease characterized by intractable seizures and unilateral brain atrophy. T cell infiltrates in affected brain tissue and the presence of circulating autoantibodies in some RE patients have indicated that RE may be an autoimmune disease. The strongest genetic links to autoimmunity reside in the MHC locus, therefore, we determined the human leukocyte antigen (HLA) class I and class II alleles carried by a cohort of 24 RE surgery cases by targeted in-depth genomic sequencing. Compared with a reference population the allelic frequency of three alleles, DQA1*04:01:01, DQB1*04:02:01, and HLA-C*07:02:01:01 indicated that they might confer susceptibility to the disease. It has been reported that HLA-C*07:02 is a risk factor for Graves disease. Further, eight patients in the study cohort carried HLA-A*03:01:01:01, which has been linked to susceptibility to multiple sclerosis. Four patients carried a combination of three HLA class II alleles that has been linked to type 1 diabetes (DQA1*05:01:01:01~DQB1*02:01:01~DRB1*03:01:01:01), and five patients carried a combination of HLA class II alleles that has been linked to the risk of contracting multiple sclerosis (DQA1*01:02:01:01, DQB1*06:02:01, DRB1*15:01:01:01). We also analyzed the diversity of αβ T cells in brain and blood specimens from 14 of these RE surgery cases by sequencing the third complementarity regions (CDR3s) of rearranged T cell receptor β genes. A total of 31 unique CDR3 sequences accounted for the top 5% of all CDR3 sequences in the 14 brain specimens. Thirteen of these sequences were found in sequencing data from healthy blood donors; the remaining 18 sequences were patient specific. These observations provide evidence for the clonal expansion of public and private T cells in the brain, which might be influenced by the RE patient’s HLA haplotype.
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DOI：
10.1038/nrrheum.2012.58
发表时间：
2012-05-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Harden JL;Hamm D;Gulati N;Lowes MA;Krueger JG
通讯作者：
Krueger JG
影响因子：
3.2
作者：
Hollenbach, Jill A.;Madbouly, Abeer;Maiers, Martin
通讯作者：
Maiers, Martin
影响因子：
11.2
作者：
Bauer, Jan;Eiger, Christian E.;Bien, Christian G.
通讯作者：
Bien, Christian G.
影响因子：
14.9
作者：
Gonzalez-Galarza FF;Christmas S;Middleton D;Jones AR
通讯作者：
Jones AR