Common Variable Immunodeficiency

Common Variable Immunodeficiency is a topic covered in the Select 5-Minute Pediatrics Topics.

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Basics

Description

  • Common variable immunodeficiency is the most common clinically important primary immunodeficiency syndrome, characterized by
    • Low IgG, IgA, and/or IgM
    • Recurrent infections
    • A wide spectrum of immunologic abnormalities, including autoimmune disease, inflammatory conditions, and the development of lymphomas
  • Other terminology for this disease include the following:
    • Acquired hypogammaglobulinemia
    • Adult-onset hypogammaglobulinemia
    • Dysgammaglobulinemia
    • Common variable hypogammaglobulinemia
  • Diagnosis of exclusion, requiring low IgG and variable reduction in IgA and/or IgM, impaired specific antibody responses

Epidemiology

  • Prevalence is estimated to be 1 in 25,000 to 1 in 66,000 in the general population.
  • Can present at any age
    • Most diagnosed between 20 and 40 years old
    • Diagnosis is usually made several years after the onset of recurrent infections (pneumonia, sinusitis, otitis).
  • A subgroup of children has been described in which the onset of disease was most often <5 years of age. This group was characterized by a relapsing and remitting course in which autoimmune disease predominated.
  • About 20–25% of patients with common variable immunodeficiency have 1 or more autoimmune conditions at time of diagnosis.
  • Affects males and females equally

Risk Factors

Genetics

  • Complex genetics, likely multifactorial
  • Rare recessive mutations described in
    • T-cell inducible costimulatory (ICOS) in one kindred, <1% of patients
    • CD19 in a few unrelated families
    • B-cell activating factor (BAFF)
    • CD20 and CD81
    • Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI, TNFRSF13B) in 8% of patients, associated with autoimmunity and lymphoid hyperplasia; heterozygous mutation more common than homozygous; significance not clear due to similar mutation found in healthy family members
  • IgA deficiency more likely in offspring of parents with common variable immunodeficiency
  • Incidence of IgA deficiency, autoimmune disease, and malignancies is increased in family members of patients with common variable immunodeficiency.

Pathophysiology

  • Main characteristic is hypogammaglobulinemia.
  • Impaired immunoglobulin and specific antibody production despite normal B cell numbers
  • Often increased proportion of immature B cells
  • Deficiency of class-switched memory B cells associated with more complex disease (autoimmunity, granulomatous disease, hypersplenism, and lymphoid hyperplasia)
  • Functional defects of both B and T lymphocytes are described.

Etiology

  • The primary immunologic defect(s) leading to this syndrome is unknown.
  • Multiple defects have been associated with common variable immunodeficiency, including the following:
    • Lack of somatic mutation within variable region genes
    • Lack of memory B cells
    • Impaired maturation, IL-12 secretion, and upregulation of costimulatory molecules by antigen-presenting cells may impair T cells, which are important for providing help to B cells for antibody production.
    • Toll-like receptor 9 (TLR9) response and expression by B cells may also be impaired. TLR signaling pathways are being investigated for their potential role in pathogenesis of common variable immunodeficiency.
  • Some genetic defects have been described but do not account for the majority of cases.

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Citation

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TY - ELEC T1 - Common Variable Immunodeficiency ID - 14174 Y1 - 2015 PB - Select 5-Minute Pediatrics Topics UR - https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14174/all/Common_Variable_Immunodeficiency ER -