Evidence map›Paper›PMID 30407753›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2019

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

Ankit Mahendra, Xingyu Yang, Shaza Abnouf, Jay R T Adolacion, Daechan Park, Sanam Soomro, Jason Roszik, Cristian Coarfa, Gabrielle Romain, Keith Wanzeck and 6 more

Abstract readEvaluation Study
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 32 citations in OpenAlex.

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  16. Characterizing the autoreactive B cell transcriptome.Nature reviews. Rheumatology · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 7 institutions in 3 countries.

Ankit MahendraUniversity of Houston, Houston, Texas.
Xingyu YangGeorgia Institute of Technology, Atlanta.
Shaza AbnoufUniversity of Houston, Houston, Texas.
Jay R T AdolacionUniversity of Houston, Houston, Texas.
Daechan ParkAjou University, Suwon, Republic of Korea.
Sanam SoomroUniversity of Houston, Houston, Texas.
Jason RoszikUniversity of Texas MD Anderson Cancer Center, Houston.
Cristian CoarfaBaylor College of Medicine, Houston, Texas.
Gabrielle RomainUniversity of Houston, Houston, Texas.
Keith WanzeckUniversity of Alabama at Birmingham.
S Louis BridgesUniversity of Alabama at Birmingham.ORCID 0000-0003-3785-1389
Amita AggarwalSanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Peng QiuGeorgia Institute of Technology, Atlanta.
Sandeep K AgarwalBaylor College of Medicine, Houston, Texas.
Chandra MohanUniversity of Houston, Houston, Texas.
Navin VaradarajanUniversity of Houston, Houston, Texas.ORCID 0000-0001-7524-8228
University of Houston · USBaylor College of Medicine · USGeorgia Institute of Technology · USUniversity of Alabama at Birmingham · USAjou University · KRSanjay Gandhi Post Graduate Institute of Medical Sciences · INThe University of Texas MD Anderson Cancer Center · US

Funding

Quantitative single-cell biomarkers of T-cells to optimize tumor immunotherapyR01CA174385 · NCI · UNIVERSITY OF HOUSTON · PI COOPER, LAURENCE J.N., VARADARAJAN, NAVIN · 2012 to 2015
$2.1M
Prostate Cancer Detection Through Urine Headspace Analysis Using Colorimetric SenR43CA180466 · NCI · ISENSE MEDICAL CORPORATION · PI RHODES, PAUL · 2014 to 2014
$150k
Cancer Prevention and Research Institute of Texas RP130570Cancer Prevention and Research Institute of Texas RP180466Melanoma Research Alliance 509800National Science Foundation 1705464NCI NIH HHS R01 CA174385United States Department of Defense CA160591Welch Foundation E-1774
6 · The paper itself

Abstract

objectiveTo obtain the comprehensive transcriptome profile of human citrulline-specific B cells from patients with rheumatoid arthritis (RA).

methodsCitrulline- 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.

resultsCitrulline-specific B cells, in comparison to citrulline-negative B cells, from patients with RA differentially expressed the interleukin-15 receptor α (IL-15Rα) 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-15Rα 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.

conclusionTo 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.

Indexed as

Arthritis, RheumatoidAutoantibodiesB-LymphocytesCytokinesErbB ReceptorsHumansLeukocytes, MononuclearReceptors, Interleukin-15Sequence Analysis, RNASignal TransductionTranscriptomeAutoantibodiesCytokinesEGFR protein, humanErbB ReceptorsIL15RA protein, humanReceptors, Interleukin-15

Identifiers

PMID30407753
PMCPMC6741783
OpenAlexW2899981011

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.