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Single-gene association between GATA-2 and autoimmune hepatitis: A novel genetic insight highlighting immunologic pathways to disease

Lookup NU author(s): Dr Venetia BigleyORCiD, Professor Matthew CollinORCiD


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Background & Aims: Autoimmune hepatitis (AIH), an immune mediated liver disease, originates as a consequence of interacting genetic and environmental risk factors. Treatment remains nonspecific and prone to side effects. Deficiencies in regulatory T cell (Treg) function are hypothesized to contribute to the pathogenesis of AIH.Methods: We describe an adult patient who presented with AIH in the context of monocytopenia. The patient was characterized by GATA2 gene sequencing, flow cytometry of peripheral blood for leucocyte subsets, ELISA for serum Flt-3 ligand, and immunohistochemistry of liver biopsy tissue.Results: Sequencing confirmed a GATA2 mutation. Peripheral Treg were absent in the context of a preserved total T cell count. Immunostaining for the Treg transcription factor FOXP3 was reduced in liver tissue as compared to a control AIH specimen. There were marked deficiencies in multiple antigen-presenting cell subsets and Flt-3 ligand was elevated. These findings are consistent with previous reports of GATA2 dysfunction.Conclusions: The association of a GATA2 mutation with AIH is previously unrecognized. GATA2 encodes a hematopoietic cell transcription factor, and mutations may manifest as monocytopenia, dendritic and B cell deficiencies, myelodysplasia, and immunodeficiency. Tregs may be depleted as in this case. Our findings provide support for the role of Tregs in AIH, complement reports of other deficiencies in T cell regulation causing AIH-like syndromes, and support the rationale of attempting to modulate the Treg axis for the therapeutic benefit of AIH patients. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Webb G, Chen YY, Li KK, Neil D, Oo YH, Richter A, Bigley V, Collin M, Adams DH, Hirschfield GM

Publication type: Article

Publication status: Published

Journal: Journal of Hepatology

Year: 2016

Volume: 64

Issue: 5

Pages: 1190-1193

Print publication date: 01/05/2016

Online publication date: 23/01/2016

Acceptance date: 19/01/2016

ISSN (print): 0168-8278

ISSN (electronic): 1600-0641

Publisher: Elsevier


DOI: 10.1016/j.jhep.2016.01.017


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