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Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-08-10 , DOI: 10.3389/fimmu.2020.02170
Roos A. W. Wennink , Aridaman Pandit , Anne-Mieke J. W. Haasnoot , Sanne Hiddingh , Viera Kalinina Ayuso , Nico M. Wulffraat , Bas J. Vastert , Timothy R. D. J. Radstake , Joke H. de Boer , Jonas J. W. Kuiper

Purpose

Patients with juvenile idiopathic arthritis (JIA) are prone to developing chronic anterior uveitis (JIA-U+). Although several risk factors for JIA-U+ have been identified, the underlying etiology is poorly understood. Histopathological studies demonstrate B cell infiltrates in eye tissues of patients with JIA-U+.

Methods

We performed transcriptome profiling of peripheral blood CD19-positive B cells taken from 14 cases with JIA-U+, 13 JIA cases without uveitis (JIA-U−), and five healthy controls. Deconvolution-based estimation was used to determine the immune cell fractions for each sample.

Results

Deconvolution results revealed that naive B cells made up on average 71% of the CD19-positive cell fractions analyzed. Differential expression analysis identified 614 differentially expressed genes (DEGs) between the groups at nominal significance and six genes at a false discovery rate of 5% (FDR < 0.05). Head-to-head comparison of all JIA-U− versus JIA-U+ revealed no DEGs in the CD19+ B cell pool (FDR < 0.05). However, principal component analysis based on a panel of key genes for B cell subsets revealed that JIA-U+ cases bifurcate into distinct clusters, characterized by markedly disparate expression for genes associated with specific memory B cell populations. CIBERSORT analysis of the overall transcriptome of the new uveitis cluster identified an increased proportion of memory B cells.

Conclusion

These data show that JIA-U− and JIA-U+ have a globally similar transcriptome considering the global peripheral CD19-positive B cell pool. However, heterogeneity in B cell memory genes among cases with uveitis suggests a role for specific memory B cell subsets in the etiology of JIA-U+.



中文翻译:

全转录组分析揭示了幼年特发性关节炎相关性葡萄膜炎患者B细胞记忆种群的异质性。

Purpose

少年特发性关节炎(JIA)患者容易发展为慢性前葡萄膜炎(JIA-U +)。尽管已经确定了JIA-U +的几种危险因素,但对潜在的病因知之甚少。组织病理学研究表明,JIA-U +患者眼组织中存在B细胞浸润​​。

Methods

我们对14例JIA-U +,13例无葡萄膜炎(JIA-U-)的JIA病例和5名健康对照的外周血CD19阳性B细胞进行了转录组分析。基于反卷积的估计用于确定每个样品的免疫细胞分数。

Results

解卷积结果显示,原始B细胞平均占所分析CD19阳性细胞分数的71%。差异表达分析确定了名义上有意义的组之间的614个差异表达基因(DEG)和错误发现率为5%的六个基因(FDR <0.05)。所有JIA-U-和JIA-U +的头对头比较显示,CD19 + B细胞池中没有DEG(FDR <0.05)。然而,基于一组针对B细胞亚群的关键基因的主成分分析显示,JIA-U +病例分叉成不同的簇,其特征是与特定记忆B细胞群体相关的基因表达明显不同。新葡萄膜炎簇的整体转录组的CIBERSORT分析确定了记忆B细胞比例的增加。

Conclusion

这些数据表明,考虑到整体外周CD19阳性B细胞池,JIA-U-和JIA-U +具有总体相似的转录组。然而,葡萄膜炎病例中B细胞记忆基因的异质性提示JIA-U +病因中特定记忆B细胞亚群的作用。

更新日期:2020-09-18
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