Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

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

(2018) Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort. The journal of allergy and clinical immunology. In practice. ISSN 2213-2201 (Electronic)

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/30240888

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 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.

Item Type: Article
Keywords: Agammaglobulinemia Common variable immunodeficiency Hyper-IgM syndrome Next-generation sequencing Primary antibody deficiencies Primary immunodeficiency Sanger sequencing
Divisions:
Journal or Publication Title: The journal of allergy and clinical immunology. In practice
Journal Index: Pubmed
Identification Number: https://doi.org/10.1016/j.jaip.2018.09.004
ISSN: 2213-2201 (Electronic)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/954

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