Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

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

(2019) Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort. Journal of Allergy and Clinical Immunology: In Practice.

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Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

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
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
Page Range: 864-878.e9
Journal or Publication Title: Journal of Allergy and Clinical Immunology: In Practice
Volume: 7
Number: 3
Publisher: American Academy of Allergy, Asthma and Immunology
Identification Number: 10.1016/j.jaip.2018.09.004
ISSN: 22132198
Depositing User: مهندس جمال محمودپور
URI: http://eprints.muk.ac.ir/id/eprint/2086

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