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Common variable immunodeficiency (CVID) is a grouping of heterogeneous diseases with the common finding of impaired antibody production.
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Morbidity is not limited to infection; in fact, noninfectious complications can be the most threatening and difficult to treat.
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Proper care of patients with CVID includes both replacement of immunoglobulin G and monitoring for CVID-associated disease on a regular basis.
Common Variable Immunodeficiency: Diagnosis, Management, and Treatment
Section snippets
Key points
Initial Evaluation
Historically, the definition of common variable immunodeficiency (CVID) focused on the predominant finding of antibody deficiency, but more recent definitions have focused on the associated clinical features frequently seen. The most cited definition of CVID was presented by the European Society for Immunodeficiency (ESID) and the Pan American Group for Immunodeficiency in 1999, and the following criteria for probable CVID were proposed: greater than 2 years of age, immunoglobulin G (IgG) and
Epidemiology
Because of the rarity of primary immunodeficiency in general, very large groups of patients with CVID have not been studied; however, there are several reports of CVID cohorts with substantial numbers of patients from which generalizations can be drawn (Table 2).13, 15, 17, 19, 20, 42, 43, 44, 45 CVID occurs equally in males and females, although, among children, boys predominate. CVID age of onset is variable, but more recent studies suggest peaks in early childhood and around the third decade
Cell Biology
Most patients with CVID have intrinsic B-cell defects. It has been known for some time that peripheral B cells from most patients with CVID produce subnormal amounts of IgG or IgM when subjected to B-cell receptor stimulation9; however, this finding may merely reflect the marked reduction of memory B cells in those patients with CVID.10 Taking into account the variability in B-cell subsets contained in peripheral blood, several groups still have identified intrinsic B-cell abnormalities,
Prognosis
The diagnosis of CVID carries a significantly increased mortality risk; however, the risk seems to be entirely contained within a subset of patients. The increased mortality risk was initially attributed to noninfectious complications in a large retrospective analysis of a European CVID registry.15 Confirming that finding, a large single-center study identified an 11-times higher risk of death among patients with CVID with noninfectious complications compared with patients with CVID with only
Concluding remarks
Over the past 60 years, CVID has emerged as the predominant class of primary antibody deficiencies. During this time period, important variation in both clinical features and underlying pathology have been identified. In fact, many patients with CVID have little in common other than meeting minimal diagnostic criteria. Nonetheless, grouping patients with antibody deficiency into this diagnostic category has allowed for the differentiation of multiple important endotypes, the study of which will
References (124)
- et al.
Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)
Clin Immunol
(1999) - et al.
Controversies in IgG replacement therapy in patients with antibody deficiency diseases
J Allergy Clin Immunol
(2013) - et al.
Secondary hypogammaglobulinemia
Immunol Allergy Clin N Am
(2001) - et al.
Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2
Clin Immunol Immunopathol
(1990) - et al.
Severe deficiency of switched memory B cells (CD27(+)IgM(−)IgD(−)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease
Blood
(2002) - et al.
Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia
Immunobiology
(2002) - et al.
The EUROclass trial: defining subgroups in common variable immunodeficiency
Blood
(2008) - et al.
Common variable immunodeficiency disorders: division into distinct clinical phenotypes
Blood
(2008) - et al.
Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts
J Allergy Clin Immunol
(2012) - et al.
Morbidity and mortality in common variable immune deficiency over 4 decades
Blood
(2012)
Genetic CD21 deficiency is associated with hypogammaglobulinemia
J Allergy Clin Immunol
Family and linkage study of selective IgA deficiency and common variable immunodeficiency
Clin Immunol Immunopathol
Genome-wide association identifies diverse causes of common variable immunodeficiency
J Allergy Clin Immunol
Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity
Am J Hum Genet
CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia
J Allergy Clin Immunol
Clinical and immunological features of common variable immunodeficiency in Mexican patients
Allergol Immunopathol (Madr)
Defective calcium signaling and disrupted CD20-B-cell receptor dissociation in patients with common variable immunodeficiency disorders
J Allergy Clin Immunol
T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency
Blood
Evaluation of CD4+CD25+FOXP3+ regulatory T cells function in patients with common variable immunodeficiency
Cell Immunol
Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients
Clin Immunol
Common variable immunodeficiency: clinical and immunological features of 248 patients
Clin Immunol
Outcome of allogeneic stem cell transplantation in adults with common variable immunodeficiency
J Allergy Clin Immunol
Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency
Clin Gastroenterol Hepatol
Hepatitis in common variable immunodeficiency
Hum Pathol
Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders
Clin Radiol
Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency
J Allergy Clin Immunol
Granulomatous- lymphocytic lung disease shortens survival in common variable immunodeficiency
J Allergy Clin Immunol
High-dose versus low-dose intravenous immunoglobulin in hypogammaglobulinaemia and chronic lung disease
Lancet
Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study
J Autoimmun
Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID)
J Autoimmun
Hematologic complications of primary immune deficiencies
Blood Rev
New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin
Clin Exp Immunol
Lymphoid proliferations of indeterminate malignant potential arising in adults with common variable immunodeficiency disorders: unusual case studies and immunohistological review in the light of possible causative events
J Clin Immunol
Multilaboratory assessment of threshold versus fold-change algorithms for minimizing analytical variability in multiplexed pneumococcal IgG measurements
Clin Vaccin Immunol
Serotype-specific anti-pneumococcal IgG and immune competence: critical differences in interpretation criteria when different methods are used
J Clin Immunol
Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects
J Clin Immunol
Variability of memory B cell markers in a cohort of common variable immune deficiency patients over 6 months
Scand J Immunol
Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study
J Clin Immunol
Clinical picture and treatment of 2212 patients with common variable immunodeficiency
J Allergy Clin Immunol
Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients
Exp Rev Clin Immunol
Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency
Nat Immunol
B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans
Proc Natl Acad Sci U S A
An antibody-deficiency syndrome due to mutations in the CD19 gene
N Engl J Med
CD20 deficiency in humans results in impaired T cell-independent antibody responses
J Clin Invest
CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency
J Clin Invest
TACI is mutant in common variable immunodeficiency and IgA deficiency
Nat Genet
Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans
Nat Genet
A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency
J Allergy Clin Immunol
Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4
Science
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