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Abstract：
BACKGROUND: Primary Sjogren\'s syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells.
METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq.
RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity.
CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.
METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq.
RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity.
CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.
摘要：
背景：原发性干燥综合征（pSS）是一种复杂的自身免疫性疾病，以唾液腺和泪腺受损为特征，具有跨多个器官表现的可能性。产生抗体的B细胞长期以来一直被认为在pSS发病机制中起着重要作用，已经鉴定出许多自身反应性抗体在pSS患者中升高。虽然一些研究试图表征pSS患者外周血B细胞的BCR库，关于腺体浸润性B细胞的库特征仍然未知。
方法：通过配对的scRNAseq和scBCRseq，我们在一小组患者中对浸润和循环B细胞的BCR谱进行了分析.我们进一步利用受体重建分析来进一步研究先前通过RNAseq分析的更广泛的pSS患者队列中的库特征。
结果：通过B细胞克隆的整合BCR和转录组分析，我们生成pSS中渗透记忆B细胞的轨迹进展模式。我们观察到pSS患者外周血和唇腺B细胞之间的BCR谱系在相对扩增方面的显着差异，同种型用法，和BCR聚类。我们进一步观察到pSS患者唇和腮腺B细胞中IgA2同种型使用的显着减少，这些分析相对于对照，以及κ/λ轻链使用与临床疾病活动之间的正相关。
结论：通过对pSS患者唾液腺的BCR库分析，我们确定了许多新的组库特征,这些特征可作为临床疾病和疾病活动的有用指标.通过将这些BCR目录收集到一个可访问的数据库中，我们希望还能够对pSS和潜在的其他自身免疫性疾病患者进行比较分析.
方法：通过配对的scRNAseq和scBCRseq，我们在一小组患者中对浸润和循环B细胞的BCR谱进行了分析.我们进一步利用受体重建分析来进一步研究先前通过RNAseq分析的更广泛的pSS患者队列中的库特征。
结果：通过B细胞克隆的整合BCR和转录组分析，我们生成pSS中渗透记忆B细胞的轨迹进展模式。我们观察到pSS患者外周血和唇腺B细胞之间的BCR谱系在相对扩增方面的显着差异，同种型用法，和BCR聚类。我们进一步观察到pSS患者唇和腮腺B细胞中IgA2同种型使用的显着减少，这些分析相对于对照，以及κ/λ轻链使用与临床疾病活动之间的正相关。
结论：通过对pSS患者唾液腺的BCR库分析，我们确定了许多新的组库特征,这些特征可作为临床疾病和疾病活动的有用指标.通过将这些BCR目录收集到一个可访问的数据库中，我们希望还能够对pSS和潜在的其他自身免疫性疾病患者进行比较分析.
