Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort
| Autor: | Asghar Aghamohammadi, Farhad Abolnezhadian, Afshin Shirkani, Arezou Rezaei, Mojgan Safari, Hans D. Ochs, Seyed Hamidreza Mortazavi, Parisa Ashournia, Amir Ali Hamidieh, Setareh Mamishi, Vassilios Lougaris, Ashraf Samavat, Hedayat Akbari, Sepideh Darougar, Akefeh Ahmadiafshar, Hamid Ahanchian, Reza Faridhosseini, Sarehsadat Ebrahimi, Arash Kalantari, Seyed Alireza Mahdaviani, Rasoul Nasiri Kalmarzi, Mahmoud Tavassoli, Reza Amin, Fatemeh Behmanesh, Hassan Abolhassani, Abbas Khalili, Marzieh Tavakol, Mohammad Hossein Eslamian, Mehrnaz Mesdaghi, Ahmad Vosughimotlagh, Abbas Fayezi, Naser Javahertrash, Soheila Aleyasin, Marzieh Heidarzadeh, Lennart Hammarström, Nima Parvaneh, Gholamreza Azizi, Nasrin Behniafard, Fatemeh Kiaee, Maziar Rahim, Mojgan Moghtaderi, Mitra Tafakoridelbari, Mohammamd Nabavi, Morteza Fallahpour, Javad Tafaroji, Reza Yazdani, Rasol Molatefi, Mahnaz Sadeghi-Shabestari, Delara Babaie, Mohammad Hassan Bemanian, Babak Negahdari, Seyed Mohammad Fathi, Taher Cheraghi, Behzad Shakerian, Mahboubeh Mansouri, Saba Arshi, Javad Ghaffari, Tooba Momen, Hossein Ali Khazaei, Behrang Taghvaei, Babak Ghalebaghi, Mohammad Ali Zamani, Alireza Khayatzadeh, Fariborz Zandieh, Masoud Movahedi, Sima Habibi, Saeed Bazregari, Nasrin Bazargan, Sara Kashef, Abbas Dabbaghzadeh, Samin Sharafian, Hossein Esmaeilzadeh, Vahid Sajedi, Mohammad Gharagozlou, Silvia Giliani, Javad Mohammadi, Behzad Darabi, Azam Mohsenzadeh, Zahra Chavoshzadeh, Bahram Bashardoust, Anahita Razaghian, Habib Soheili, Roya Sherkat, Alireza Shafiei, Alessandro Plebani, Nima Rezaei, Mohammadreza Zandkarimi, Maryam Khoshkhui, Iraj Mohammadzadeh, Farahzad Jabbari-Azad |
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| Rok vydání: | 2018 |
| Předmět: |
hyper-IgM syndrome
Adult Diarrhea Male Hyper IgM syndrome Sanger sequencing Adolescent Primary antibody deficiencies Primary immunodeficiency agammaglobulinemia common variable immunodeficiency next generation sequencing CD40 Ligand X-linked agammaglobulinemia Hyper-IgM Immunodeficiency Syndrome Severity of Illness Index Hypogammaglobulinemia 03 medical and health sciences Young Adult 0302 clinical medicine Agammaglobulinemia Activation-induced (cytidine) deaminase Agammaglobulinaemia Tyrosine Kinase Immunology and Allergy Bruton's tyrosine kinase Medicine Humans Meningitis 030212 general & internal medicine Child Immunodeficiency Genetic Association Studies biology business.industry Immunoglobulin mu-Chains Common variable immunodeficiency medicine.disease Common Variable Immunodeficiency 030228 respiratory system Child Preschool Immunology Mutation biology.protein Female business Poliomyelitis |
| Zdroj: | The journal of allergy and clinical immunology. In practice. 7(3) |
| ISSN: | 2213-2201 |
| Popis: | 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 mu 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 mu 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 mu 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. |
| Databáze: | OpenAIRE |
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