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- W4313385802 abstract "Abstract B cells are important in the pathogenesis of rheumatoid arthritis (RA). By utilizing a flow-cytometric assay to reliably detect the low frequency of autoreactive B cells (ABC) in the blood of RA patients, we performed RNA sequencing of citrulline-specific ABCs and compared them with hemaglutinin (HA) specific B cells. To the best of our knowledge, this is the first complete transcriptome map of human ABCs in autoimmunity, and our data shows a specific up regulation of amphiregulin (AREG) (q-value = 3.1×10−12, fold-change = 250); a member of the EGF growth factor of ligands. Also, the receptor signaling pathways associated with AREG including EGF mediated signaling (FDR q-value = 0.06) and the NRG1 mediated signaling (FDR q-value = 0.03) were enriched, supporting an important role for AREG. Consistent with the well-recognized role of TNF in RA, our RNA-seq data revealed highly significant enrichment of both the TNF pathway (FDR q-value = 0.02) and genes that are targets of TNF (FDR q-value = 0.08) in ABCs from RA patients. Comparisons of our differential expression gene analyses with known risk loci of RA (SNPs) identified genes with decreased expression including TNFAIP3 (leading to inflammatory responses), and REL (anti-apoptotic); and increased expression including CCR6 (maturation and differentiation), and ETS1 (development and maturation) within ABCs than HA specific B cells. Ig sequencing of ABC show normal mutational targeting frequencies but increased somatic hymermutation. In aggregate, our results indicate that the pro-inflammatory nature of IL15 and TNF mediated signaling might promote a feed-forward loop promoting the altered differentiation of ABCs through the AREG-TNF signaling axis, which in turn promotes inflammation." @default.
- W4313385802 created "2023-01-06" @default.
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- W4313385802 date "2016-05-01" @default.
- W4313385802 modified "2023-09-29" @default.
- W4313385802 title "New insights into rheumatoid arthritis by whole transcriptome profiling of autoreactive B cells" @default.
- W4313385802 doi "https://doi.org/10.4049/jimmunol.196.supp.47.15" @default.
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