Diagnosis of DOCK8 deficiency using Flow cytometry Biomarkers: an Egyptian Center experience

Safa S Meshaal; Rabab E El Hawary; Alia Eldash; Bodo Grimbacher; Nadezhda Camacho-Ordonez; Dalia S Abd Elaziz; Nermeen M Galal; Jeannette A Boutros; Shereen M Shawky; Aisha M Elmarsafy

doi:10.1016/j.clim.2018.07.011

Diagnosis of DOCK8 deficiency using Flow cytometry Biomarkers: an Egyptian Center experience

Clin Immunol. 2018 Oct:195:36-44. doi: 10.1016/j.clim.2018.07.011. Epub 2018 Jul 24.

Affiliations

¹ Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address: safa.meshaal@kasralainy.edu.eg.
² Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
³ Center for Chronic Immunodeficiency, University Hospital, Medical Faculty, Albert-Ludwigs University, Freiburg, Germany; Department of Immunology, Royal Free Hospital, University College London, London, UK.
⁴ Center for Chronic Immunodeficiency, University Hospital, Medical Faculty, Albert-Ludwigs University, Freiburg, Germany.
⁵ Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

PMID: 30048691
DOI: 10.1016/j.clim.2018.07.011

Abstract

In the past few years, several genes were shown to be implicated in various forms of the Hyper Immunoglobulin E syndrome. The present study is the first to describe a cohort of DOCK8 deficiency patients from Egypt. The study included 15 patients with features of combined immunodeficiency (CID) suggestive of DOCK8 deficiency. Flow cytometry was used for evaluation of DOCK8 expression and studying different immunological characteristics of those patients including evaluation of Th17, Tregs, T and B lymphocytes differentiation and the effect of the DOCK8 deficiency on the activation of the STAT3. Diagnosis was confirmed by mutational analysis. Profound defects in Th17 cells and Tregs were observed in all patients with impaired STAT3 phosphorylation, indicating that DOCK8 plays a pivotal role in the STAT3 signaling pathway. These findings together with decrease in memory B cells and defective DOCK8 expression by flow cytometry can confirm the diagnosis.

Keywords: AR-HIES; DOCK8; Flow cytometry; Th17; pSTAT3.

MeSH terms

B-Lymphocytes / immunology*
Biomarkers / metabolism*
Cell Differentiation
Child
Child, Preschool
Cohort Studies
Egypt
Female
Flow Cytometry / methods*
Guanine Nucleotide Exchange Factors / genetics
Guanine Nucleotide Exchange Factors / metabolism*
Humans
Immunologic Memory
Job Syndrome / diagnosis*
Male
Phosphorylation / genetics
STAT3 Transcription Factor / metabolism
Sequence Deletion / genetics
Signal Transduction
T-Lymphocytes, Regulatory / immunology*
Th17 Cells / immunology*

Substances

Biomarkers
DOCK8 protein, human
Guanine Nucleotide Exchange Factors
STAT3 Transcription Factor
STAT3 protein, human