Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Yazdani, Reza and Abolhassani, Hassan and Kiaee, Fatemeh and Habibi, Sima and Azizi, Gholamreza and Tavakol, Marzieh and Chavoshzadeh, Zahra and Mahdaviani, Seyed Alireza and Momen, Tooba and Gharagozlou, Mohammad and Movahedi, Masoud and Hamidieh, Amir Ali and Behniafard, Nasrin and Nabavi, Mohammamd and Bemanian, Mohammad Hassan and Arshi, Saba and Molatefi, Rasol and Sherkat, Roya and Shirkani, Afshin and Amin, Reza and Aleyasin, Soheila and Faridhosseini, Reza and Jabbari-Azad, Farahzad and Mohammadzadeh, Iraj and Ghaffari, Javad and Shafiei, Alireza and Kalantari, Arash and Mansouri, Mahboubeh and Mesdaghi, Mehrnaz and Babaie, Delara and Ahanchian, Hamid and Khoshkhui, Maryam and Soheili, Habib and Eslamian, Mohammad Hossein and Cheraghi, Taher and Dabbaghzadeh, Abbas and Tavassoli, Mahmoud and Kalmarzi, Rasoul Nasiri and Mortazavi, Seyed Hamidreza and Kashef, Sara and Esmaeilzadeh, Hossein and Tafaroji, Javad and Khalili, Abbas and Zandieh, Fariborz and Sadeghi-Shabestari, Mahnaz and Darougar, Sepideh and Behmanesh, Fatemeh and Akbari, Hedayat and Zandkarimi, Mohammadreza and Abolnezhadian, Farhad and Fayezi, Abbas and Moghtaderi, Mojgan and Ahmadiafshar, Akefeh and Shakerian, Behzad and Sajedi, Vahid and Taghvaei, Behrang and Safari, Mojgan and Heidarzadeh, Marzieh and Ghalebaghi, Babak and Fathi, Seyed Mohammad and Darabi, Behzad and Bazregari, Saeed and Bazargan, Nasrin and Fallahpour, Morteza and Khayatzadeh, Alireza and Javahertrash, Naser and Bashardoust, Bahram and Zamani, Mohammadali and Mohsenzadeh, Azam and Ebrahimi, Sarehsadat and Sharafian, Samin and Vosughimotlagh, Ahmad and Tafakoridelbari, Mitra and Rahim, Maziar and Ashournia, Parisa and Razaghian, Anahita and Rezaei, Arezou and Samavat, Ashraf and Mamishi, Setareh and Khazaei, Hossein Ali and Mohammadi, Javad and Negahdari, Babak and Parvaneh, Nima and Rezaei, Nima and Lougaris, Vassilios and Giliani, Silvia and Plebani, Alessandro and Ochs, Hans D. and Hammarström, Lennart and Aghamohammadi, Asghar (2019) Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort. The Journal of Allergy and Clinical Immunology: In Practice, 7 (3). 864-878.e9. ISSN 22132198

Full text not available from this repository.
Official URL:


Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Item Type: Article
Subjects: QW Microbiology and Immunology
Divisions: Faculty of Medicine > Basic Sciences Academic Groups > Department of Immunology
Depositing User: zeynab . bagheri
Date Deposited: 17 May 2020 07:45
Last Modified: 17 May 2020 07:45

Actions (login required)

View Item View Item