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高通量测序分析 B 细胞和 T 细胞受体揭示 IgA 肾病中保守的受体库。

Integrated analysis of B‑cell and T‑cell receptors by high‑throughput sequencing reveals conserved repertoires in IgA nephropathy.

机构信息

Clinical Medical Research Center of Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.

Lab Center of Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China.

出版信息

Mol Med Rep. 2018 May;17(5):7027-7036. doi: 10.3892/mmr.2018.8793. Epub 2018 Mar 20.

DOI:10.3892/mmr.2018.8793
PMID:29568935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5928659/
Abstract

Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3 clones were expressed at very low frequencies, and the composition of clone types in patients with IgAN was skewed; the majority of clones were unique, and only 12 BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a significantly higher frequency in patients with IgAN (P<0.001). There were also certain conserved amino acid residues between unique clones or groups, and the residues GMDV, EQY and EQF were recurring only in the IgAN group. In addition, some VDJ gene recombinations indicated great variation between groups, including 4 high‑frequency VDJ gene recombinations in the IgAN patients (P<0.001). Immune repertoires provide novel information, and conserved BCR/TCR CDR3 clones and VDJ gene recombinations with great variation may be potential therapeutic targets for IgAN patients.

摘要

免疫球蛋白 A 肾病(IgAN)是一种与免疫失调相关的肾小球疾病,了解 B-/-T-细胞受体(BCR/TCR)对于开发特异性免疫治疗干预可能具有重要价值。本研究通过多重聚合酶链反应、高通量测序和生物信息学分析,从 IgAN 患者和健康对照中分离 B 细胞和 T 细胞,分析 BCR/TCR 互补决定区(CDR)3 的组成。本研究结果显示,BCR/TCR CDR3 克隆以非常低的频率表达,且 IgAN 患者的克隆类型组成存在偏倚;大多数克隆是独特的,仅有 12 个 BCR 和 228 个 TCR CDR3 克隆是公共的,其中 16 个在 IgAN 患者中的表达频率显著更高(P<0.001)。独特克隆或组之间也存在某些保守的氨基酸残基,且残基 GMDV、EQY 和 EQF 仅在 IgAN 组中反复出现。此外,一些 VDJ 基因重组表明组间存在很大差异,包括 IgAN 患者中 4 个高频 VDJ 基因重组(P<0.001)。免疫受体库提供了新的信息,具有高度变异性的保守 BCR/TCR CDR3 克隆和 VDJ 基因重组可能是 IgAN 患者的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/38700e7ef060/MMR-17-05-7027-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/9ab2e007eab7/MMR-17-05-7027-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/6be54505946e/MMR-17-05-7027-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/64c803a993ad/MMR-17-05-7027-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/2769687a3dcc/MMR-17-05-7027-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/aa9f34fe4709/MMR-17-05-7027-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/38700e7ef060/MMR-17-05-7027-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/9ab2e007eab7/MMR-17-05-7027-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/6be54505946e/MMR-17-05-7027-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/64c803a993ad/MMR-17-05-7027-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/2769687a3dcc/MMR-17-05-7027-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/aa9f34fe4709/MMR-17-05-7027-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7689/5928659/38700e7ef060/MMR-17-05-7027-g05.jpg

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本文引用的文献

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Significance of clinical and morphological prognostic risk factors in IgA nephropathy: follow-up study of comparison patient groups with and without renoprotection.IgA肾病临床及形态学预后危险因素的意义:有无肾脏保护作用的对比患者组的随访研究
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