Data_Sheet_1_Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated.xlsx (419.26 kB)

Data_Sheet_1_Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis.xlsx

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posted on 17.09.2020, 04:43 by 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+.

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