Beyond Autoantibodies: Biologic Roles of Human Autoreactive B Cells in Rheumatoid Arthritis Revealed by RNA?Sequencing

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dc.contributor.authorMahendra, Ankit
dc.contributor.authorYang, Xingyu
dc.contributor.authorAbnouf, Shaza
dc.contributor.authorAdolacion, Jay R.T.
dc.contributor.authorPark, Daechan
dc.contributor.authorSoomro, Sanam
dc.contributor.authorRoszik, Jason
dc.contributor.authorCoarfa, Cristian
dc.contributor.authorRomain, Gabrielle
dc.contributor.authorWanzeck, Keith
dc.contributor.authorBridges, Louis Jr. S.
dc.contributor.authorAggarwal, Amita
dc.contributor.authorQiu, Peng
dc.contributor.authorAgarwal, Sandeep K.
dc.contributor.authorMohan, Chandra
dc.contributor.authorVaradarajan, Navin
dc.date.accessioned2020-03-11T17:05:43Z
dc.date.available2020-03-11T17:05:43Z
dc.date.issued2017-06
dc.description.abstractObjective:To obtain the comprehensive transcriptome profile of human citrulline?specific B cells from patients with rheumatoid arthritis (RA). Methods:Citrulline? and hemagglutinin?specific B cells were sorted by flow cytometry using peptide–streptavidin conjugates from the peripheral blood of RA patients and healthy individuals. The transcriptome profile of the sorted cells was obtained by RNA?sequencing, and expression of key protein molecules was evaluated by aptamer?based SOMAscan assay and flow cytometry. The ability of these proteins to effect differentiation of osteoclasts and proliferation and migration of synoviocytes was examined by in vitro functional assays. Results:Citrulline?specific B cells, in comparison to citrulline?negative B cells, from patients with RA differentially expressed the interleukin?15 receptor ? (IL?15R?) gene as well as genes related to protein citrullination and cyclic AMP signaling. In analyses of an independent cohort of cyclic citrullinated peptide–seropositive RA patients, the expression of IL?15R? protein was enriched in citrulline?specific B cells from the patients’ peripheral blood, and surprisingly, all B cells from RA patients were capable of producing the epidermal growth factor ligand amphiregulin (AREG). Production of AREG directly led to increased migration and proliferation of fibroblast?like synoviocytes, and, in combination with anti–citrullinated protein antibodies, led to the increased differentiation of osteoclasts. Conclusion:To the best of our knowledge, this is the first study to document the whole transcriptome profile of autoreactive B cells in any autoimmune disease. These data identify several genes and pathways that may be targeted by repurposing several US Food and Drug Administration–approved drugs, and could serve as the foundation for the comparative assessment of B cell profiles in other autoimmune diseases.
dc.identifier.citationCopyright 2018 Arthritis and Rheumatism. This is a pre-print version of a published paper that is available at: http://ev7su4gn4p.search.serialssolutions.com/?id=doi:10.1002/art.40772&sid=wiley&iuid=7265662&date=2019&jtitle=Arthritis+&+Rheumatology=&volume=71&genre=article&atitle=Beyond+Autoantibodies:+Biologic+Roles+of+Human+Autoreactive+B+Cells+in+Rheumatoid+Arthritis+Revealed+by+RNA%E2%80%90Sequencing&spage=529&issue=4&title=Arthritis+&issn=2326-5191&epage=541. Recommended citation: Mahendra, Ankit, Xingyu Yang, Shaza Abnouf, Jay RT Adolacion, Daechan Park, Sanam Soomro, Jason Roszik et al. "Beyond Autoantibodies: Biologic Roles of Human Autoreactive B Cells in Rheumatoid Arthritis Revealed by RNA?Sequencing." Arthritis & Rheumatology 71, no. 4 (2019): 529-541. doi:10.1101/144121 . This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission.
dc.identifier.urihttps://hdl.handle.net/10657/6194
dc.language.isoen_US
dc.publisherArthritis and Rheumatism
dc.titleBeyond Autoantibodies: Biologic Roles of Human Autoreactive B Cells in Rheumatoid Arthritis Revealed by RNA?Sequencing
dc.typeArticle

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