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

Yazdani, R. and Abolhassani, H. and Kiaee, F. and Habibi, S. and Azizi, G. and Tavakol, M. and Chavoshzadeh, Z. and Mahdaviani, S.A. and Momen, T. and Gharagozlou, M. and Movahedi, M. and Hamidieh, A.A. and Behniafard, N. and Nabavi, M. and Bemanian, M.H. and Arshi, S. and Molatefi, R. and Sherkat, R. and Shirkani, A. and Amin, R. and Aleyasin, S. and Faridhosseini, R. and Jabbari-Azad, F. and Mohammadzadeh, I. and Ghaffari, J. and Shafiei, A. and Kalantari, A. and Mansouri, M. and Mesdaghi, M. and Babaie, D. and Ahanchian, H. and Khoshkhui, M. and Soheili, H. and Eslamian, M.H. and Cheraghi, T. and Dabbaghzadeh, A. and Tavassoli, M. and Kalmarzi, R.N. and Mortazavi, S.H. and Kashef, S. and Esmaeilzadeh, H. and Tafaroji, J. and Khalili, A. and Zandieh, F. and Sadeghi-Shabestari, M. and Darougar, S. and Behmanesh, F. and Akbari, H. and Zandkarimi, M. and Abolnezhadian, F. and Fayezi, A. and Moghtaderi, M. and Ahmadiafshar, A. and Shakerian, B. and Sajedi, V. and Taghvaei, B. and Safari, M. and Heidarzadeh, M. and Ghalebaghi, B. and Fathi, S.M. and Darabi, B. and Bazregari, S. and Bazargan, N. and Fallahpour, M. and Khayatzadeh, A. and Javahertrash, N. and Bashardoust, B. and Zamani, M. and Mohsenzadeh, A. and Ebrahimi, S. and Sharafian, S. and Vosughimotlagh, A. and Tafakoridelbari, M. and Rahim, M. and Ashournia, P. and Razaghian, A. and Rezaei, A. and Samavat, A. and Mamishi, S. and Khazaei, H.A. and Mohammadi, J. and Negahdari, B. and Parvaneh, N. and Rezaei, N. and Lougaris, V. and Giliani, S. and Plebani, A. and Ochs, H.D. and Hammarström, L. and Aghamohammadi, A. (2019) Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort. Journal of Allergy and Clinical Immunology: In Practice, 7 (3). 864-878.e9.

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Abstract

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. © 2018 American Academy of Allergy, Asthma & Immunology

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: activation induced cytidine deaminase; CD40 ligand; immunoglobulin mu chain; poliomyelitis vaccine, adolescent; adult; agammaglobulinemia; Article; atypical immunodeficiency; centromeric instability; child; chronic diarrhea; clinical feature; cohort analysis; common variable immunodeficiency; comparative study; controlled study; disease severity; face dysmorphia; female; gene mutation; genetic disorder; genotype phenotype correlation; heavy chain disease; human; humoral immune deficiency; hyper IgM syndrome; lipopolysaccharide responsive beige like anchor deficiency; lung disease; major clinical study; male; meningitis; next generation sequencing; poliomyelitis; Sanger sequencing; X linked agammaglobulinemia
Subjects: Biochemistry, Genetics and Molecular Biology
Immunology and Microbiology
Divisions: Faculty of Medicine > Basic Sciences > Department of Microbiology & Immunology
Depositing User: ART . editor
Date Deposited: 20 May 2019 12:07
Last Modified: 20 May 2019 12:07
URI: http://eprints.kaums.ac.ir/id/eprint/3706

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