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Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.
- Source :
-
The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2019 Mar; Vol. 7 (3), pp. 864-878.e9. Date of Electronic Publication: 2018 Sep 19. - Publication Year :
- 2019
-
Abstract
- Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses.<br />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.<br />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.<br />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).<br />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.<br /> (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Agammaglobulinaemia Tyrosine Kinase genetics
CD40 Ligand genetics
Child
Child, Preschool
Diarrhea genetics
Diarrhea mortality
Female
Genetic Association Studies
Humans
Immunoglobulin mu-Chains genetics
Male
Meningitis genetics
Meningitis mortality
Mutation
Poliomyelitis genetics
Poliomyelitis mortality
Severity of Illness Index
Young Adult
Agammaglobulinemia genetics
Agammaglobulinemia mortality
Common Variable Immunodeficiency genetics
Common Variable Immunodeficiency mortality
Hyper-IgM Immunodeficiency Syndrome genetics
Hyper-IgM Immunodeficiency Syndrome mortality
Subjects
Details
- Language :
- English
- ISSN :
- 2213-2201
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The journal of allergy and clinical immunology. In practice
- Publication Type :
- Academic Journal
- Accession number :
- 30240888
- Full Text :
- https://doi.org/10.1016/j.jaip.2018.09.004