Investigating the Variation of TREC/KREC in Combined Immunodeficiencies

Leila Shakerian; Maryam Nourizadeh; Mohsen Badalzadeh; Mohammad Reza Fazlollahi; Raheleh Shokouhi Shoormasti; Shiva Saghafi; Behnaz Esmaeili; Zahra Alizadeh; Stephan Borte; Massoud Houshmand; Lennart Hammarström; Zahra Pourpak

doi:10.18502/ijaai.v20i4.6950

Leila Shakerian Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Maryam Nourizadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Mohsen Badalzadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Reza Fazlollahi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Raheleh Shokouhi Shoormasti Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Shiva Saghafi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Behnaz Esmaeili Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Zahra Alizadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Stephan Borte Immuno Deficiency Center Leipzig (IDCL), Hospital St. Georg GmbH Leipzig, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany
Massoud Houshmand Department of Medical Genetics National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
Lennart Hammarström Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
Zahra Pourpak Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v20i4.6950

Keywords: Neonatal screening; Primary immunodeficiency disorders; Real-time polymerase chain reaction

Abstract

T-cell receptor excision circles (TREC)/Kappa-deleting recombination excision circles (KREC) assay has been recently recognized for detecting patients with primary (T- and/or B-cell) immunodeficiency (PID). We aimed to investigate the alterations of these biomarkers in some combined immunodeficiency patients compared to the healthy controls in different age groups.

TREC and KREC were assessed in a total of 82 PID patients, most of them with exact genetic diagnosis (3 months to 42 years); using quantitative real-time-polymerase chain reaction (PCR). Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 with DOCK8 deficiency, 4 with signal transducer and activator of transcription 3 (STAT3) deficiency, and 8 children with unknown genetic defects), Wiskott-Aldrich syndrome (WAS) (n=20), purine nucleoside phosphorylase (PNP)deficiency(n=1), dedicator of cytokinesis2 (DOCK2) deficiency (n=1), recombinase activating gene1 (RAG1) deficiency (n=1).

Very low to zero amounts of TREC and/or KREC were detected in 14 out of 23 cases of common variable immunodeficiency (CVID), 14 out of 17 cases of AT, 8 out of 20 cases of WAS, 6 out of 7 cases of DOCK8-deficiency patients, 4 out of 8 cases of HIES with unknown genetic defects and all patients with defects in DOCK2, PNP, and RAG1. STAT3-deficient patients were normal for both biomarkers. All patients showed a significant difference in both markers compared to age-matched healthy controls.

Our findings highlight that apart from severe types of T/B cell defects, this assay can also be used for early diagnosis the patients with late-onset of disease and even PIDs without a positive family history.