T-cell mitochondrial dysfunction and lymphopenia in DOCK2-deficient patients

To the Editor: Dedicator of cytokinesis 2 (DOCK2) is a guanine nucleotide exchange factor expressed predominantly in hematopoietic cells that activates the Rac GTPases.1,2 Biallelic mutations in DOCK2 cause a combined immunodeficiency with T-cell lymphopenia and impaired T-cell activation.1,3 The me...

Full description

Saved in:
Bibliographic Details
Published in:Journal of allergy and clinical immunology 2019-07, Vol.144 (1), p.306-309.e2
Main Authors: Alosaimi, Mohammed F., Shendi, Hiba, Beano, Abdallah, Stafstrom, Kelsey, El Hawary, Rabab, Meshaal, Safa, Galal, Nermeen, Pai, Sung-Yun, El-Marsafy, Aisha, Geha, Raif S., Chou, Janet
Format: Article
Language:English
Subjects:
Activation
Age
Antigens
CD4 antigen
CD8 antigen
Cell activation
Cytokinesis
Cytomegalovirus
Defects
Female
GTPase-Activating Proteins - deficiency
GTPase-Activating Proteins - genetics
Guanine
Guanine nucleotide exchange factor
Guanine Nucleotide Exchange Factors - deficiency
Guanine Nucleotide Exchange Factors - genetics
Homeostasis
Humans
Immunodeficiency
Immunoglobulins
Immunologic Deficiency Syndromes - genetics
Immunologic Deficiency Syndromes - immunology
Infant
Infections
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphopenia
Male
Membrane potential
Metabolism
Mitochondria
Mitochondria - immunology
Mutation
Patients
Protein expression
Respiration
T-Lymphocytes - immunology
Viral infections
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To the Editor: Dedicator of cytokinesis 2 (DOCK2) is a guanine nucleotide exchange factor expressed predominantly in hematopoietic cells that activates the Rac GTPases.1,2 Biallelic mutations in DOCK2 cause a combined immunodeficiency with T-cell lymphopenia and impaired T-cell activation.1,3 The mechanisms underlying the T-cell lymphopenia associated with DOCK2 deficiency are incompletely understood. Because of the importance of the Rac GTPases in maintaining mitochondrial homeostasis,4,5 we investigated mitochondrial function in 2 unrelated patients with novel DOCK2 mutations abrogating protein expression. [...]to our DOCK2-deficient patients, CD4+ and CD8+ T cells robustly increased membrane potential after T-cell activation (see Fig E1). [...]chronic antigenic T-cell activation cannot solely explain the defective mitochondrial membrane potential seen in DOCK2-deficient T cells. Because Patient 1 had normal numbers of B cells, we were able to generate an EBV-transformed lymphoblastoid B-cell line (BLCL) from her PBMCs.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2019.02.020