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Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency.

Dang, Tarana Singh, Willet, Joseph D P, Griffin, Helen R, Morgan, Neil V, O'Boyle, Graeme, Arkwright, Peter D, Hughes, Stephen M, Abinun, Mario, Tee, Louise J, Barge, Dawn, Engelhardt, Karin R, Jackson, Michael, Cant, Andrew J, Maher, Eamonn R, Koref, Mauro Santibanez, Reynard, Louise N, Ali, Simi and Hambleton, Sophie (2016) Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency. Journal of clinical immunology, 36 (2). pp. 117-22. ISSN 1573-2592

Item Type: Article



To investigate the clinical and functional aspects of MST1 (STK4) deficiency in a profoundly CD4-lymphopenic kindred with a novel homozygous nonsense mutation in STK4. Although recent studies have described the cellular effects of murine Mst1 deficiency, the phenotype of MST1-deficient human lymphocytes has yet to be fully explored. Patient lymphocytes were therefore investigated in the context of current knowledge of murine Mst1 deficiency.


Genetic etiology was identified by whole exome sequencing of genomic DNA from two siblings, combined with linkage analysis in the wider family. MST1 protein expression was assessed by immunoblotting. The ability of patient lymphocytes to adhere to ICAM-1 under flow conditions was measured, and transwell assays were used to assess chemotaxis. Chemokine receptor expression was examined by flow cytometry and receptor signalling by immunoblotting.


A homozygous nonsense mutation in STK4 (c.442C > T, p.Arg148Stop) was found in the patients, leading to a lack of MST1 protein expression. Patient leukocytes exhibited deficient chemotaxis after stimulation with CXCL11, despite preserved expression of CXCR3. Patient lymphocytes were also unable to bind effectively to immobilised ICAM-1 under flow conditions, in keeping with a failure to develop high affinity binding.


The observed abnormalities of adhesion and migration imply a profound trafficking defect among human MST1-deficient lymphocytes. By analogy with murine Mst1 deficiency and other defects of leucocyte trafficking, this is likely to contribute to immunodeficiency by impairing key aspects of T-cell development and function such as positive selection in the thymus, thymic egress and immune synapse formation in the periphery.

10.1007%2Fs10875-016-0232-2.pdf - Published Version

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Depositing User: Graeme O'Boyle


Item ID: 9294
Identification Number:
ISSN: 1573-2592
Official URL:

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ORCID for Graeme O'Boyle: ORCID iD

Catalogue record

Date Deposited: 09 May 2018 10:24
Last Modified: 18 Dec 2019 16:06


Author: Graeme O'Boyle ORCID iD
Author: Tarana Singh Dang
Author: Joseph D P Willet
Author: Helen R Griffin
Author: Neil V Morgan
Author: Peter D Arkwright
Author: Stephen M Hughes
Author: Mario Abinun
Author: Louise J Tee
Author: Dawn Barge
Author: Karin R Engelhardt
Author: Michael Jackson
Author: Andrew J Cant
Author: Eamonn R Maher
Author: Mauro Santibanez Koref
Author: Louise N Reynard
Author: Simi Ali
Author: Sophie Hambleton

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences


Sciences > Biomedical Sciences

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