Common variable immunodeficiency: A new look at an old disease

Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
The Lancet (Impact Factor: 45.22). 09/2008; 372(9637):489-502. DOI: 10.1016/S0140-6736(08)61199-X
Source: PubMed


Primary immunodeficiencies comprise many diseases caused by genetic defects primarily affecting the immune system. About 150 such diseases have been identified with more than 120 associated genetic defects. Although primary immunodeficiencies are quite rare in incidence, the prevalence can range from one in 500 to one in 500 000 in the general population, depending on the diagnostic skills and medical resources available in different countries. Common variable immunodeficiency (CVID) is the primary immunodeficiency most commonly encountered in clinical practice, and appropriate diagnosis and management of patients will have a significant effect on morbidity and mortality as well as financial aspects of health care. Advances in diagnostic laboratory methods, including B-cell subset analysis and genetic testing, coupled with new insights into the molecular basis of immune dysfunction in some patients with CVID, have enabled advances in the clinical classification of this heterogeneous disease.

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    • "Humoral immunodeficiency (HID) is another common cause of recurrent infections of the upper and lower respiratory tract. Common variable immunodeficiency disorder (CVID) is a rare (prevalence around 1/ 75.000) entity, characterized by hypogammaglobulinemia, defective specific antibody production and an increased susceptibility to recurrent infections [2]. Selective IgA deficiency and isolated IgG subclass deficiency (IgG 2 or IgG 3 deficiency) on the other hand are found more frequently, and in some patients they are the only identifiable cause of recurrent respiratory tract infections. "
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    ABSTRACT: Background: Primary ciliary dyskinesia (PCD) and humoral mmunodeficiency (HID) are both rare disorders which cause recurrent upper and lower respiratory tract infections. Objective: To examine the concurrence of PCD and HID in a patient cohort with known PCD. Methods: Retrospective review of the patient files. Results: We describe 11 patients of a cohort of 168 patients with PCD (6.5%) with a combina-tion of PCD and some form of HID. The patients all presented with typical clinical symptoms for PCD, however the role of the concomitant immunological abnormalities is not clear. Conclusion: PCD and HID coincided in 6.5% of the patients. We suggest that a common patho-physiological pathway results in both disorders.
    Full-text · Article · Jun 2014 · Respiratory medicine
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    • "Common variable immunodeficiency (CVID), despite being a relatively rare condition, represents the most commonly encountered primary immunodeficiency in clinical practice associated with clinically significant antibody failure [1]. This intrinsic antibody deficiency may appear at any age and presents enormous heterogeneity [1, 2]. "
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    ABSTRACT: Late onset combined immunodeficiency (LOCID) is a recently described variant of common variable immunodeficiency (CVID), involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to have Pneumocystis jiroveci pneumonia (PJP), subsequently complicated by recurrent hospital-acquired Pseudomonas aeruginosa pneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID). Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses.
    Full-text · Article · Mar 2014 · Case Reports in Medicine
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    • "Common variable immunodeficiency (CVID) is one of the most common primary immune deficiency and is characterized by low levels of IgG and IgA [1], [2]. Several genetic mutations associated with CVID have been identified, but in many cases the exact cause is unknown [2]. "
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    ABSTRACT: Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.
    Full-text · Article · Oct 2013 · PLoS ONE
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