Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CVID is frequently diagnosed in male and female individuals with hypogammaglobulinaemia of unknown aetiology. To examine the possibility that sporadic male cases with X-linked agammaglobulinaemia (XLA), which is caused by mutations in the Bruton's tyrosine kinase (Btk) gene, might be misregistered as having CVID, we employed a flow cytometric test to identify XLA in hypogammaglobulinaemic males registered as CVID in the Japanese Immunodeficiency Registry. From 30 male cases registered as having CVID between 1992 and 1998, we selected 21 males with low or unreported peripheral B cell counts. Blood samples could be obtained from 11 patients and their mothers. Using flow cytometric analysis, the Btk-deficient status in monocytes was demonstrated in seven out of nine cases with decreased numbers of peripheral B cells. The diagnosis of XLA was confirmed in each of the seven patients by demonstration of Btk gene mutations in the patients or cellular mosaicism in the mother. This study demonstrates misregistration of XLA as CVID.
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PMID:Detection of Bruton's tyrosine kinase mutations in hypogammaglobulinaemic males registered as common variable immunodeficiency (CVID) in the Japanese Immunodeficiency Registry. 1084 31

Physicians in the United States who treat patients with primary immunodeficiency were contacted to identify subjects who had been infected with hepatitis C due to exposure to contaminated intravenous immunoglobulin (IVIg) in 1993-1994. From this survey we gathered information on 58 PCR-positive hepatitis C-infected patients; 37 had CVID, 9 had XLA, 5 were IgG subclass deficient, 4 were antibody deficient with normal immunoglobulin levels, 2 had SCID after BMT, and 1 had B cell linker deficiency. Of the 58 subjects, 30 had been treated with IFN-alpha in combination with ribavirin in 5 cases, and 26 other subjects were not treated. Of those who were treated, 11 (37%) resolved the infection and became PCR-negative; of the 26 who were not treated, 5 (19%) have resolved the infection, outcomes not significantly different. Patients 20 years of age or younger had a significantly better outcome compared to those older than age 20 (P = 0.02). Five subjects of the 58 have had a liver transplantation, a sixth has had two transplants, and 10 (17%) of the group have died. This survey demonstrates the heterogeneity of the clinical outcome in subjects with primary immunodeficiency who contracted hepatitis C due to viral contamination of IVIg.
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PMID:Outcome of intravenous immunoglobulin-transmitted hepatitis C virus infection in primary immunodeficiency. 1172 20

Seventeen patients with antibody immunodeficiency (9 subclass IgG immunodeficiencies, 8 common variable immunodeficiencies) and clinically unambiguous immunodeficiency symptomatology participated in the study with 14 healthy donors. The patients were given regular intravenous immunoglobulin (IVIG) infusions with Endobulin. Blood was collected before and 7 days after infusion of the usual IVIG dose. Mononuclear cells were isolated from peripheral blood (PBMC) of the patients by Ficoll-Paque gradient centrifugation. In order to monitor the ability to inhibit or activate polyclonal production of immunoglobulins in vitro, we stimulated PBMC with pokeweed mitogen (PWM) and with a mixture of pokeweed mitogen + concanavalin A (PWM+ConA). We found that an immunomodulatory effect of IVIG persists in vitro even one week after infusion. Polyclonally stimulated IgA and IgM production was suppressed by IVIG infusion mainly in patients with IgG subclass deficiency. The positive stimulatory effect of IVIG infusion on IgG production was confirmed. The IgG production increased in vitro after infusion in both groups of patients and was significantly higher than in healthy donors. Co-stimulation of PWM-stimulated cells with ConA caused an inhibition of immunoglobulin release in normal healthy donors. The infusion supported the capability of ConA to inhibit IgG production in vitro in patients with IgG subclass deficiency, whereas an increase in IgG production with PWM+ConA stimulation after infusion was found in CVID patients. We assume that lymphocytes activated by ConA produce suppressive factors, which can be affected by the IVIG infusion and which can have both an immunostimulatory and an immunosuppressive effect.
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PMID:Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiency. 1207 73

Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly.
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PMID:The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency. 1589 36

The tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. We found that 4 of 19 unrelated individuals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD) had a missense mutation in one allele of TNFRSF13B (encoding TACI). One of the four individuals with CVID had a single nucleotide insertion in the other TNFRSF13B allele. None of these mutations were present in 50 healthy subjects. TNFRSF13B mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals that we studied. B cells from individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype switching. These results suggest that TACI mutations can result in CVID and IgAD.
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PMID:TACI is mutant in common variable immunodeficiency and IgA deficiency. 1604 3

Common variable immunodeficiency (CVID) is the most prevalent human primary immunodeficiency requiring medical attention. Until recently, the only known genetic defect specific to CVID was the inducible costimulatory receptor (ICOS) deficiency, which accounts for less than 1% of the patients. Recently, mutations in the TNF receptor family member transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), which mediates isotype switching in B cells, were found to be present in 10% to 20% of patients with CVID. Mutations in TACI were also found in relatives of patients with CVID who had IgA deficiency (IgAD), as well as in a patient with isolated IgAD. In the majority of patients described to date, only one TACI allele is mutated, showing an autosomal dominant transmission of the disease. B cells from individuals with TACI mutations did not produce IgG and IgA in response to the TACI ligand a proliferation-inducing ligand (APRIL), probably reflecting impaired isotype switching. These results suggest that TACI mutations can lead to CVID and IgAD.
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PMID:Molecular basis of common variable immunodeficiency. 1663 Sep 28

Mutations of the gene encoding the TNF receptor family member transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), TNFSRF13B, have recently been described in patients with common variable immunodeficiency (CVID). We report the case of a man with CVID in association with a heterozygous TACI gene mutation (C104R) who had a highly unusual, invasive, polyclonal CD8+ T-cell lymphoproliferation resulting in massive hepatosplenomegaly and causing renal impairment because of infiltration. Although lymphoproliferation is well described in CVID, the key features in this patient included the T-cell origin of the lymphoproliferation, its polyclonal nature, its infiltration into multiple organs, and the presence of the TACI gene mutation.
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PMID:TACI mutation with invasive polyclonal CD8+ T-cell lymphoproliferation in a patient with common variable immunodeficiency. 1663 Sep 28

We have analysed data from 150 patients initially classified as having CVID. About 10% had laboratory abnormalities suggesting known single gene disorders (eg: hyper-IgM syndrome), and in a few a genetic defect has been confirmed. We have attempted to sub-classify the remaining patients by analysis of their circulating lymphocytes. B lymphocyte markers have been used to estimate the numbers of circulating immature and class switched B cells; there is an association between the presence of high relative numbers of immature circulating B cells, splenomegaly and autoimmune disease. About 25% of CVID patients have a moderate CD4+ T lymphopenia, sometimes with a relative expansion of CD8+ T cells. About 30% of CVID patients have persistent relatively high levels of circulating CD8+ T cells binding immunogenic peptides from EBV or CMV. Many of these patients also have high relative numbers of circulating CD8+ perforin positive T cells, and there is evidence that these cells may be responsible for neutropenia or inflammatory bowel disease in some patients. The clinical spectrum of CVID is diverse, with some patients suffering from few infections, and over 50% have evidence of structural lung damage. About 25% of UK patients have chronic inflammation in various organs, particularly the lungs, liver and spleen, often with granulomatous changes. Steroids are used to treat many of the patients with chronic inflammatory complications, although trials are in progress with anti-TNF agents. The incidence of these inflammatory complications is different between countries, being rare in Sweden. Attempts to correlate clinical phenotypes with the laboratory abnormalities described above have been disappointing, suggesting that unknown genetic factors unrelated to the cause of the immunodeficiency determine the complications; attempts to identify some of these factors will be discussed. Finally a provisional scheme to sub classify CVID patients according to lymphocyte abnormalities will be presented, the purpose being to focus the screening of candidate genes causing CVID to specific subsets of patients.
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PMID:Clinical and Immunological Spectrum of Common Variable Immunodeficiency (CVID). 1730

Nutrition is an important factor that influences immunity, and nutritional deficiencies can impair resistance to infections. Malnutrition is the most common cause of immunodeficiency worldwide. Trace elements such as zinc, selenium, iron, and copper can influence several components of immunity. Primary antibody deficiency disorders are a group of disorders characterized by an unusual susceptibility to infections and malnutrition. Impaired nutritional status has been reported in immunodeficient patients. The aim of this study was to determine anthropometric indices and trace elements status in these patients. Thirty-eight children (28 males, 10 females, aged 2-18 years) with primary antibody deficiency referring to Children's Medical Center of Tehran University of Medical Science were enrolled in this research. Primary immunodeficiency disorders consisting of CVID, XLA, IgA deficiency, IgG subclass deficiency, and hyper IgM were assessed. Anthropometric indices, comprised of height, weight that were measured and body mass index (BMI) was calculated. Height-for-age (HAZ), weight-for-height (WHZ) and weight-for-age (WAZ) were determined according to Z-score to study mild, moderate and severe malnutrition. Serum copper, zinc, selenium and iron levels were measured by an atomic absorption spectrometer. The most common disorders were CVID 52.5% and X-linked agammaglobulinaemia 27.5%. Based on BMI measurements 21.1% of patients had malnutrition. According to HAZ, 13.2%, 13.2% and 36.8% had severe, moderate and mild malnutrition, respectively. According to WAZ, 10.5%, 18.4% and 28.6% had severe, moderate and mild malnutrition, respectively. Regarding to WHZ, 14.3% and 28.6% had moderate and mild malnutrition, respectively. Low selenium levels and high copper levels were observed in 37.5% and 70.3%, respectively. Anthropometric data showed that the frequency of malnutrition in these patients was higher than the CDC standard. Low serum selenium levels and high serum copper levels were observed, suggesting further research is needed on these parameters. Most of the patients had serum zinc and iron levels within the normal range. It is recommeded that clinical immunologists and nutritionists should make a collective effort to provide these patients with standard or specialized diets so as to decrease the risk of infection.
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PMID:A study of malnutrition in Iranian patients with primary antibody deficiency. 1730 13

B cell activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL), and their receptors BAFF receptor (BAFFR), B cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI) are involved in the regulation of B cell homeostasis and differentiation. BAFF overexpression leads to systemic lupus erythematosus (SLE) in mice and elevated BAFF levels have been observed in human SLE and mouse models for SLE. Furthermore, genetic inactivation of TACI in mice results in a SLE-like phenotype. Based on our recent finding that TACI is mutated in patients with common variable immunodeficiency, of whom more than 30% suffer from autoimmune conditions, we analyzed TACI in humans with SLE. Sequence analysis of TNFRSF13b/TACI in 119 unrelated SLE patients revealed four variants: R20C in exon 1, R72H in exon 3, the silent variation c.327 G > A in exon 3, and A181E in exon 4. No significant association with any of these variants was found, when compared to the frequencies of the variants in a healthy control cohort. Furthermore, the mutated alleles R20C and R72H did not segregate with the SLE phenotype in familial cases of SLE. Thus, our evaluation of the coding region of TNFRSF13b/TACI did not reveal any deleterious or disease-associated mutations.
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PMID:Sequence analysis of TNFRSF13b, encoding TACI, in patients with systemic lupus erythematosus. 1746 55


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