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- Title
Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis.
- Authors
Wennink, Roos A. W.; Pandit, Aridaman; Haasnoot, Anne-Mieke J. W.; Hiddingh, Sanne; Kalinina Ayuso, Viera; Wulffraat, Nico M.; Vastert, Bas J.; Radstake, Timothy R. D. J.; de Boer, Joke H.; Kuiper, Jonas J. W.
- Abstract
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+.
- Subjects
B cells; CELL populations; JUVENILE idiopathic arthritis; UVEITIS; FALSE discovery rate
- Publication
Frontiers in Immunology, 2020, Vol 11, pN.PAG
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2020.02170