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Hypogammaglobulinemia in children: a warning sign to look deeply?

Karina Mescouto de Melo1, Maria Isabel de Moraes-Pinto1, Luís E C Andrade2

  • 1Department of Pediatrics, Escola Paulista de Medicina, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil.

APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
|September 21, 2017
PubMed

Insights

Children with common variable immunodeficiency (CVID) show early immune defects, while those with unclassified hypogammaglobulinemia (UH) exhibit distinct B-cell changes. Parents of CVID children may have familial B-cell disturbances.

Area of Science:

  • Immunology
  • Pediatric immunology
  • Cellular immunology

Background:

  • Common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH) are primary immunodeficiency disorders characterized by low antibody levels.
  • Understanding lymphocyte subset phenotypes and functions is crucial for diagnosing and managing these conditions in children.

Purpose of the Study:

  • To investigate the phenotypic and functional characteristics of lymphocytes in pediatric CVID and UH.
  • To analyze B-cell subsets in non-consanguineous parents of children with CVID to explore potential familial links.

Main Methods:

  • Flow cytometry was used to analyze CD4, CD8 T-cell, and B-cell subpopulations in children and adults.
  • In vitro stimulation with phytohemagglutinin (PHA) and tetanus toxoid was performed to assess T-cell cytokine production (IFN-γ).

Main Results:

  • Children with CVID had reduced switched memory B cells and decreased CD8+ IFN-γ-producing T cells post-stimulation.
  • Children with UH showed increased total CD4+ T-cell counts and elevated transitional B cells.
  • Parents of CVID children exhibited lower naive B cells and higher memory B cells compared to controls.

Conclusions:

  • Pediatric CVID is associated with an early combined immune defect.
  • A potential familial B-cell disturbance may be present in pediatric CVID cases.
  • Distinct lymphocyte profiles differentiate CVID and UH in children, suggesting different underlyingpathogenic mechanisms.

Keywords:
Hypogammaglobulinemiachildrencytokinelymphocytesprimary immunodeficiency

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