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Concept: Common variable immunodeficiency

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OBJECTIVE: Common Variable Immunodeficiency Disorder (CVID) is a complex disorder that predisposes patients to recurrent and severe infections. Immunophenotypic classification schemes were developed to categorise CVID patients into phenotypic and prognostic groups based on different memory B cell subsets. Whether the B cell subset analysis is stable over time has not been investigated. METHODS: B cell phenotyping in CVID patients (n=15) and sex- and age-matched controls (n=26) were carried out according to the three B cell classifications. CVID patients were evaluated monthly over six months. Controls were assessed once during the study. RESULTS: We scored how often each patient was assigned to the same group within each classification. The Freiburg classification assigned patients to the same group at a rate of 73% and the Paris classification at 88%. The EUROclass classification of smB- vs smB+ was at 90%. The two sub-classifications [(smB-21low or smB-21norm) and transitional B] were at 87% and 97% respectively. The level of naïve B cells measured in all CVID patients during the 6 month evaluation was the most stable B cell subset. CONCLUSION: We conclude that all classifications systems show considerable variability but the EUROclass classification was the most reliable scheme for our 15 CVID and 26 healthy cohorts. Our results indicate that phenotypic classifications within CVID will be difficult while there is variability of commonly used assays.

Concepts: Immune system, Gene, B cell, Immunodeficiency, Memory B cell, Primary immunodeficiency, Common variable immunodeficiency

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Common variable immunodeficiency (CVID) is an inherited disease characterized by hypogammaglobulinaemia and impaired humoural immunoresponse and is mainly associated with recurrent infections of the airway and the digestive tract. An 18-year old female with a diagnosis of CVID associated with a devastating necrotizing periodontitis, ultimately resulting in complete destruction of the periodontium and loss of all teeth, is reported. Clinical, biochemical, microbiological and radiographic examinations are presented. The report highlights the likely importance of immunoglobulin replacement and intensive dental hygiene in CVID patients, and the devastating effect of non-compliance in such patients.

Concepts: Immune system, Disease, Infectious disease, Immunodeficiency, Oral hygiene, Primary immunodeficiency, Common variable immunodeficiency, Hypogammaglobulinemia

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Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells.

Concepts: DNA, Genetics, Genetic disorder, Somatic hypermutation, Immunodeficiency, Primary immunodeficiency, Common variable immunodeficiency, Hypogammaglobulinemia

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Common variable immunodeficiency (CVID) is characterized clinically by inadequate quantity and quality of serum immunoglobulins with increased susceptibility to infections, resulting in significant morbidity and mortality. Only a few genes have been uncovered, and the genetic background of CVID remains elusive to date for the majority of patients.

Concepts: Immune system, Bacteria, Mortality rate, Virus, Immunodeficiency, Primary immunodeficiency, Common variable immunodeficiency

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Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by antibody deficiency, poor humoral response to antigens, and recurrent infections. To investigate the molecular cause of CVID, we carried out exome sequence analysis of a family diagnosed with CVID and identified a heterozygous frameshift mutation, c.2564delA (p.Lys855Serfs(∗)7), in NFKB2 affecting the C terminus of NF-κB2 (also known as p100/p52 or p100/p49). Subsequent screening of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second heterozygous nonsense mutation, c.2557C>T (p.Arg853(∗)), in one simplex case. Affected individuals in both families presented with an unusual combination of childhood-onset hypogammaglobulinemia with recurrent infections, autoimmune features, and adrenal insufficiency. NF-κB2 is the principal protein involved in the noncanonical NF-κB pathway, is evolutionarily conserved, and functions in peripheral lymphoid organ development, B cell development, and antibody production. In addition, Nfkb2 mouse models demonstrate a CVID-like phenotype with hypogammaglobulinemia and poor humoral response to antigens. Immunoblot analysis and immunofluorescence microscopy of transformed B cells from affected individuals show that the NFKB2 mutations affect phosphorylation and proteasomal processing of p100 and, ultimately, p52 nuclear translocation. These findings describe germline mutations in NFKB2 and establish the noncanonical NF-κB signaling pathway as a genetic etiology for this primary immunodeficiency syndrome.

Concepts: Immune system, Antibody, Protein, Genetics, Mutation, Evolution, Primary immunodeficiency, Common variable immunodeficiency

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Generic health status quality of life (QoL) instruments have been used in patients with common variable immune deficiency (CVID). However, by their nature, these tools may over- or underestimate the impact of diseases on an individual’s QoL.

Concepts: Life, Quality, Quality of life, Gross domestic product, Immunodeficiency, Primary immunodeficiency, Human Development Index, Common variable immunodeficiency

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Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID. We integrate this evidence into a model describing a role for the gut microbiota in the maintenance of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to the development of new diagnostic tools and therapeutic targets.

Concepts: Immune system, Inflammation, Bacteria, Gut flora, Rheumatoid arthritis, Immunodeficiency, Primary immunodeficiency, Common variable immunodeficiency

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Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders.

Concepts: Immune system, Lymphocyte, Diseases and disorders, Immunodeficiency, Lymphoproliferative disorders, Immune system disorders, Primary immunodeficiency, Common variable immunodeficiency

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Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. As symptoms of CVID are usually heterogeneous and unspecific, diagnosis and follow-up of CVID can be challenging. In light of this, a broad review of advances in management and treatment of CVID is performed here in order to reach a distinct protocol. However, it should be noted that owing to the nature of the disease, it can only be treated symptomatically but not cured. There is little evidence to guide appropriate or universal guidelines to improve the current status of management of the disease. The most satisfactory treatments of CVID could be achieved by the use of immunoglobulin replacement, antibiotics, immunosuppressants and hematopoietic stem cell transplantation. This review is written based on the importance of clinical surveillance of asymptomatic CVID cases and early recognition of different clinical complications. Moreover, for each complication, appropriate interventions for improving outcomes are mentioned.

Concepts: Immune system, Medicine, Epidemiology, Medical terms, Hematopoietic stem cell, Immunodeficiency, Primary immunodeficiency, Common variable immunodeficiency

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Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis.

Concepts: DNA, Gene, Genetics, Gene expression, T cells, Immunodeficiency, Primary immunodeficiency, Common variable immunodeficiency