Measuring Dedicator of Cytokinesis 8 (DOCK8) Expression  as a Flow Cytometry Biomarker for DOCK8 Deficiency Detection

Maryam  Moradi; Mahsa Yousefpour  Marzbali; Nazanin  Nazari; Zahra  Chavoshzadeh; Seyed Alireza  Mahdaviani; Mahnaz  Sadeghi-Shabestari; Nima  Rezaei

doi:10.18502/ijaai.v24i6.20158

Maryam Moradi Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Mahsa Yousefpour Marzbali Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Nazanin Nazari Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Zahra Chavoshzadeh Department of Allergy and Clinical Immunology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Seyed Alireza Mahdaviani St. Giles Laboratory of Human Genetics of Infectious Disease, The Rockefeller University, New York, NY, USA
Mahnaz Sadeghi-Shabestari Immunology Research Center of Tabriz, Mardaniazar Children Hospital of Tabriz, Tabriz University of Medical Sciences, Tabriz, Iran
Nima Rezaei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v24i6.20158

Keywords: Flow cytometry; Hyper IgE; Immunodeficiencies; Inborn errors of immunity

Abstract

The autosomal recessive form of hyperimmunoglobulin E syndrome (AR-HIES), caused by mutations in the DOCK8 (Dedicator of Cytokinesis 8) gene, presents a wide range of clinical manifestations and phenotypically overlaps with several types of combined immunodeficiency disorders characterized by elevated serum IgE levels. Due to the high rates of morbidity and mortality, as well as the potential curability through hematopoietic stem cell transplantation (HSCT), early and accurate differential diagnosis of this syndrome is crucial for optimal management and improved prognosis. Flow cytometry tests can be beneficial for early diagnosis of many inborn errors of immunity (IEIs), including this syndrome. This study, conducted for the first time on Iranian patients, investigated the expression of the DOCK8 protein.

DOCK8 expression was assessed by flow cytometry in 14 patients (6 males and 8 females) with
a clinical diagnosis of DOCK8 deficiency. The diagnosis was ultimately confirmed through genetic
testing.

The results showed that DOCK8 expression in patients was significantly lower compared to the healthy control group.

Flow cytometric evaluation of DOCK8 protein expression offers a rapid and efficient
diagnostic method with a sensitive detection range suitable for many cases. This approach can facilitate the diagnosis of DOCK8 deficiency, thereby enabling timely and effective disease management.