Common variable immune deficiency (CVID) presenting as an autoimmune disease: role of memory B cells

doi:10.1016/j.autrev.2007.11.024

Autoimmunity Reviews

Volume 7, Issue 4, February 2008, Pages 309-312

https://doi.org/10.1016/j.autrev.2007.11.024 Get rights and content

Abstract

Common variable immunodeficiency (CVID) is a clinically heterogeneous disorder. Most often patients present with recurrent sinopulmonary infections, although it may present with autoimmune manifestations. Immune cytopenias, particularly thrombocytopenia and hemolytic anemia, are the most commonly observed. While the pathophysiology of CVID remains elusive, in many patients it may be due to an intrinsic B cell defect. Memory B cells (CD27⁺) in particular, have been noted to correlate with certain aspects of the disease. High numbers of IgM⁺ memory B cells appear to correlate with the presence of infections, whereas decreased numbers of switched memory B cells correlate with lower serum IgG levels and increased rates of autoimmune features. Because of these defects in the memory B cell compartment, there is a greater potential risk for infection and related complications. Review of the literature suggests that splenectomy should be avoided in patients with immune cytopenia and CVID and that serum immunoglobulins should be obtained in patients presenting with immune cytopenias to screen for CVID.

Section snippets

Take home messages

•
CVID is the most common symptomatic primary immunodeficiency
•
CVID may present with autoimmune disease, most commonly an immune cytopenia
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Decreased numbers of IgM⁺ memory cells and anti-pneumococcal antibodies may correlate with increased risk for infections
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Decreased numbers of switched memory cells may correlate best with autoimmunity
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Splenectomy in CVID patients with immune cytopenias poses a potential greater risk of infection from encapsulated bacteria
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Serum immunoglobulins should be checked

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Citation Excerpt :
Paradoxically, autoimmune diseases are also associated with immune deficiency and infections. For instance, at least two-thirds of patients with common variable immunodeficiency exhibit signs of autoimmune diseases [4–7]. In addition, patients with primary immune deficiency, such as DiGeorge syndrome, also exhibit signs of autoimmunity [8–12].
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Aunque pueda parecer paradójico, las inmunodeficiencias primarias y la secundaria a infección por VIH frecuentemente se complican con enfermedades autoinmunes. Esto debido a la desregulación del sistema inmune y a la activación policlonal debida a infecciones recurrentes.
Se revisan diversas enfermedades autoinmunes y autoanticuerpos asociados con ambos tipos de inmunodeficiencias.
Las enfermedades autoinmunes pueden ser la primera manifestación de una inmunodeficiencia, por lo que deben estudiarse especialmente si la enfermedad autoinmune es atípica. Las patologías más frecuentemente asociadas son las citopenias autoinmunes y los enfermedades reumatológicas.
Debe realizarse una exclusión completa de las infecciones coincidentes o posiblemente causantes de complicaciones autoinmunes antes de iniciar tratamientos específicos para ellas.
Although it may seem paradoxical, primary immunodeficiencies and HIV immunodeficiency are frecuently complicated by autoimmune conditions.
This is because of the immune system disregulation and polyclonal activation due to recurrent infections.
We review various autoimmune diseases and autoantibodies associated with both types of immunodeficiencies.
Autoimmune diseases my be the first manifestation of an immunodeficiency, so we should screen for it, specially if this autoimmune disease is atypical. The most frecuent disease associated with immunodeficiencies are autoimmune cytopenias and rheumatologic disorders.
A through exclusion of infections coincident with or possibly causative of autoimmune complication should be undertaken before initiating specific treatments for autoimmune disease in this patients.
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2010, Autoimmunity Reviews
Citation Excerpt :
Clues to the pathophysiology of a condition can often be found in considering other disease states in which it occurs. Autoimmune cytopenias have been described in T cell disorders including Digeorge syndrome and HIV [31,32], as well as B cell disorders such as common variable immunodeficiency and chronic lymphocytic leukemia [33,34]. In fact, cytopenias are the most common manifestation of autoimmunity in all primary immunodeficiencies [35], and have also been reported in other systemic autoimmune conditions [36].
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2009, Autoimmunity Reviews
Citation Excerpt :
Disease manifestations are very heterogeneous and associate infections, systemic granulomatosis, autoimmune manifestations, lymphoproliferation and gastrointestinal disease. Biological analyses reveal hypogammaglobulinemia, a normal B cell count in most of the cases and a variable T cell phenotype [21]. Autoimmune manifestations occur in about 22% of CVID patients [20,22] (Table 1).
Autoimmune manifestations have long been perceived as paradoxical in patients with primary immune deficiencies (PID). However, a defect in the mechanisms of control of self-reactive B and T cells may favour these manifestations.
Three PID are defined by the occurrence of autoimmune manifestations: APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy), autoimmune lymphoproliferative syndrome (ALPS) and IPEX syndrome (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In these conditions, organ specific autoimmune diseases such as type 1 diabetes mellitus or Hashimoto's thyroiditis are prominently encountered.
Several other PID such as common variable immunodeficiency (CVID), Good syndrome and hyper-IgM syndrome are associated with a wide variety of autoimmune manifestations, mainly autoimmune cytopenias. Thus, autoimmune manifestations have been reported in 22% of patients with CVID, increasing to 50% in the subgroup of patients with systemic granulomatosis.
Complement deficiencies involving components of the classical pathway are associated with systemic lupus erythematosus (SLE). Homozygous C2 deficiency, which is the most frequent hereditary deficiency in complement classical pathway components, is associated with SLE in 10% of the cases. Complete C1q and C4 deficiencies are less frequent but associated with a higher prevalence of SLE.
Patients with common variable immunodeficiency complicated by autoimmune phenomena have lymphopenia and reduced treg, Th17, and NK cells
2021, Journal of Clinical Medicine

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Common variable immune deficiency (CVID) presenting as an autoimmune disease: role of memory B cells

Abstract

Section snippets

Take home messages

Clin Immunol

J Allergy Clin Immunol

Blood

Clin Immunol

Semin Arthritis Rheum

J Autoimmun

Allergol Immunopathol

Immunity