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Juvenile idiopathic arthritis associated with a mutation in GATA3

dc.contributor.authorPatrick, Anna E.
dc.contributor.authorWang, Wei
dc.contributor.authorBrokamp, Elly
dc.contributor.authorGraham, Thomas Brent
dc.contributor.authorAune, Thomas M.
dc.contributor.authorDuis, Jessica B.
dc.identifier.citationPatrick AE, Wang W, Brokamp E, Graham TB, Aune TM, Duis JB. Juvenile idiopathic arthritis associated with a mutation in GATA3. Arthritis Res Ther. 2019;21(1):156. Published 2019 Jun 25. doi:10.1186/s13075-019-1946-3en_US
dc.description.abstractBackgroundGATA3 is a transcription factor that is important during development and plays a role in differentiation and activity of immune cells, particularly T cells. Abnormal T cell function is found in autoimmune arthritis. We present the first known case of autoimmune arthritis associated with a novel GATA3 mutation.MethodsWhole exome sequencing of the proband was performed on a clinical basis. Peripheral blood mononuclear cells (PBMCs) were collected from the proband, healthy sibling, and parent. cDNA prepared from RNA was analyzed with polymerase chain reaction and Sanger sequencing. Intracellular proteins were assessed by immunoblot of PBMC homogenates. GATA3 in vitro activity was measured in HeLa cell cultures expressing a mammalian expression vector containing GATA3 or mutants generated by site-directed mutagenesis. GATA3 transcriptional activity was examined using a luciferase reporter assay system. T helper cell ex vivo function was evaluated by stimulating PBMCs to differentiate into effector T cells along Th0, Th1, Th2, and Th17 lineages, and re-stimulating effector cells to secrete cytokines. Cytokine production was measured by enzyme-linked immunosorbent assay.ResultsThe proband is the first known case of autoimmune arthritis associated with a mutation in GATA3. The proband M401VfsX106 protein is expressed and has a dominant negative function on GATA3 transcriptional activity. The proband PBMCs have markedly increased differentiation along the Th1 and Th17 pathways, with decreased differentiation along the Th2 pathway. Unexpectedly, Th0 cells from the proband express high levels of IFN.ConclusionsOur research presents the first known case of autoimmune arthritis associated with a mutation in GATA3. This work expands the phenotypic spectrum of GATA3 mutations. It reveals the novel insight that decreased and altered GATA3 activity coincides with autoimmune arthritis. This work suggests that modulation of GATA3 may be a therapeutic approach for patients with autoimmune arthritis.en_US
dc.description.sponsorshipThis work was supported by grants from the National Institute of Allergy and Infectious Disease (R01 AI044924) and the National Institute of General Medical Sciences (T32 GM007569) of the National Institutes of Health and the Childhood Arthritis and Rheumatology Research Alliance (CARRA)-Arthritis Foundation.en_US
dc.publisherArthritis Research & Therapyen_US
dc.rights© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
dc.subjectAutoimmune arthritisen_US
dc.subjectJuvenile idiopathic arthritisen_US
dc.subjectT cellen_US
dc.titleJuvenile idiopathic arthritis associated with a mutation in GATA3en_US

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