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Common Variable Immunodeficiency (common + variable_immunodeficiency)
Selected AbstractsDecrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiencyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009J. Horn Summary Common variable immunodeficiencies (CVID) are a heterogeneous group of antibody deficiency disorders complicated by autoimmune, lymphoproliferative and/or granulomatous manifestations, suggesting variations in immunoregulation. We sought to quantify regulatory CD4 T cells (Treg cells) in the blood of CVID patients and to correlate the frequency with clinical manifestations and classification subgroups. Blood samples from 99 CVID patients in Freiburg, London and Sydney, who had been phenotyped clinically and stratified according to their memory B cell phenotype (Freiburg and Paris classification schemes), were analysed for the proportion of Treg cells, defined either as CD25+/forkhead box P3 (FoxP3)+, CD25+/CD127low/FoxP3+ or CD25+/CD127low CD4+ T cells, and results compared with 49 healthy controls. Irrespective of the phenotype used to define them, there was a significant decrease in the Treg cell proportion in patients with granulomatous disease and immune cytopenias. This allowed the definition of a subgroup of CVID patients with abnormally low Treg cells, which had a higher rate of these two manifestations as well as autoimmune disease in general. There was also a significant reduction in the proportion of Treg cells in the Freiburg group Ia compared with other CVID patients and controls, but there were no differences between the Paris groups. The reduction in Treg cells in subsets of CVID patients may be relevant to their clinical manifestations, and may contribute to our understanding of the pathogenesis of CVID complications. [source] Impaired nutritional status in common variable immunodeficiency patients correlates with reduced levels of serum IgA and of circulating CD4+ T lymphocytesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2001M. Muscaritoli Background Common variable immunodeficiency (CVI) is a primary defect of the immune system. Infections, persistent diarrhoea and malabsorption may result in malnutrition, which may in turn contribute to increased morbidity. In this paper, the prevalence of malnutrition in CVI was evaluated. Patients and methods Forty CVI patients (20 male, 20 female, aged 17,75 years) underwent anthropometric measurements from which body mass index, arm fat and muscle area were calculated. Body mass index values <,18·5 and arm fat and muscle area values <,10th percentile were considered indicative of malnutrition. Patients were divided into four groups according to circulating CD4+ T cells (lower or greater than 300 µL,1) and serum immunoglobulin A (IgA) levels (detectable and undetectable). Results Body mass index <,18·5, arm fat and muscle area <,10th percentile were observed in 23%, 58% and 44%, respectively, of patients. Lower values of body mass index, arm fat and muscle area were more frequent in patients with low CD4+ cells and undetectable IgA. Low arm fat values were more frequent in patients with diarrhoea (P = 0·03). Infectious episodes were more frequent in undetectable IgA than in detectable IgA patients (P = 0·04). Conclusions Anthropometric measurements revealed an increased rate of malnutrition in CVI patients, particularly in those with low CD4+ and undetectable IgA, suggesting that selected CVI subjects could be considered for standard or specialized nutritional support. [source] Common variable immunodeficiency: 20-yr experience at a single centrePEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2009Ma Pilar Llobet Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It can present at any age in patients with a history of recurrent bacterial infections, with or without a family history of other primary immunodeficiencies (PID), and shows a wide range of clinical manifestations and immunological data. Diagnosis is based on low IgG, IgM and/or IgA levels. Delayed diagnosis and therapy can lead to bronchiectasis and malabsorption. The aim of this study was to describe a paediatric population diagnosed of CVID and its evolution in the population. Memory B-cell (MB) classification carried out in these patients was correlated with clinical manifestations and outcome. Clinical and immunological data of 22 CVID children under 18 yr treated at our centre between 1985 and 2005 are presented. Immunological studies included those for diagnosis and MB quantification. Differences in form of presentation, familial incidence and MB classification were reviewed. A statistical descriptive analysis was made. Infections were the commonest manifestation, affecting mainly respiratory (19/22) and gastrointestinal (10/22) tracts. Bronchiectasis was present in seven cases, and detected prior to CVID diagnosis in five. Replacement therapy led to a significant reduction in the number of infections. Severe complications appeared mostly in patients without MB. Patients of the same family share the same MB group. Family members had also been diagnosed of CVID in seven cases. Early diagnosis and therapy are essential to improve outcome in these patients. MB studies are useful in children to orient prognosis and further genetic studies. [source] Translational Mini-Review Series on Immunodeficiency: Molecular defects in common variable immunodeficiencyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. Bacchelli Summary Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10,15% of all cases of CVID and it is highly likely that further genetic defects will be identified. [source] Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiencyAPMIS, Issue 3 2002Zuzana Krátká 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. [source] Peripheral neuropathy associated with common variable immunodeficiencyEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2000A. J. Larner We report a patient with common variable immunodeficiency (CVID) who developed an axonal sensorimotor polyneuropathy, a hitherto unreported association to our knowledge. These conditions may be linked at the pathogenetic level, since some CVID patients are prone to the development of autoimmune disease. [source] Non-functional immunoglobulin G transcripts in a case of hyper-immunoglobulin M syndrome similar to type 4IMMUNOLOGY, Issue 2 2004John M. Darlow Summary 86% of immunoglobulin G (IgG) heavy-chain gene transcripts were found to be non-functional in the peripheral blood B cells of a patient initially diagnosed with common variable immunodeficiency, who later developed raised IgM, whereas no non-functionally rearranged transcripts were found in the cells of seven healthy control subjects. All the patient's IgM heavy-chain and , light-chain transcripts were functional, suggesting that either non-functional rearrangements were being selectively class-switched to IgG, or that receptor editing was rendering genes non-functional after class-switching. The functional ,-chain sequences showed a normal rate of somatic hypermutation while non-functional sequences contained few somatic mutations, suggesting that most came from cells that had no functional gene and therefore were not receiving signals for hypermutation. However, apoptosis of peripheral blood lymphocytes was not impaired. No defects have been found in any of the genes currently known to be responsible for hyper-IgM syndrome but the phenotype fits best to type 4. [source] Severe chronic neutropenia in Chinese children in Hong KongJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2001TF Leung Objective: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed. Methodology: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong. Results: The median (range) age of the patients at initial presentation was 6.5 months (4 days,19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 × 109 /L and 0.06 × 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency. Conclusions: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections. [source] Allergic asthma in patients with common variable immunodeficiencyALLERGY, Issue 4 2010R. C. Agondi To cite this article: Agondi RC, Barros MT, Rizzo LV, Kalil J, Giavina-Bianchi P. Allergic asthma in patients with common variable immunodeficiency. Allergy 2010; 65: 510,515. Abstract Background:, Many patients with common variable immunodeficiency (CVID) have a clinical history suggestive of allergic respiratory disease. However, in such individuals, the prevalence of asthma and the role of atopy have not been well established. The objective of this study was to evaluate pulmonary function and identify asthma in patients with CVID. We also investigated the role of IgE as a trigger of asthma in these patients. Methods:, Sixty-two patients diagnosed with CVID underwent spirometry, as well as skin prick testing and in vitro determination of serum-specific IgE levels for aeroallergens, together with bronchial provocation with histamine and allergen. Results:, The most common alteration identified through spirometry was obstructive lung disease, which was observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62 patients had a clinical history suggestive of allergic asthma. By the end of the study, asthma had been diagnosed in nine (14.5%) patients and atopy had been identified in six (9.7%). In addition, allergic asthma had been diagnosed in four patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical history suggestive of the diagnosis). Conclusion:, In this study, CVID patients testing negative for specific IgE antibodies and suspected of having allergic asthma presented a positive response to bronchial provocation tests with allergens. To our knowledge, this is the first such study. When CVID patients with a history suggestive of allergic asthma test negative on traditional tests, additional tests designed to identify allergic asthma might be conducted. [source] Regression of systemic lupus erythematosus after development of an acquired Toll-like receptor signaling defect and antibody deficiencyARTHRITIS & RHEUMATISM, Issue 9 2009Marcella Visentini Toll-like receptor 9 (TLR-9) and TLR-7 may have a role in the production of anti-DNA and anti-RNA autoantibodies, respectively, but murine models do not clearly demonstrate their contribution to the development of systemic lupus erythematosus (SLE). Herein we describe a patient with SLE who had long-lasting remission of her autoimmune disease after development of an antibody deficiency resembling common variable immunodeficiency (CVID). After CVID had developed, anti,double-stranded DNA antibodies disappeared, although antinuclear antibodies remained positive for >10 years. In vitro studies revealed that the patient's B cells proliferated poorly and failed to differentiate into plasmablasts after stimulation of either TLR-9 or TLR-7, providing evidence for an acquired defect of the signaling pathway downstream of these TLRs. These observations suggest, although indirectly, that signaling through TLR-9 and TLR-7 is important in the pathogenesis of human SLE, and indicate that investigation of potential treatment strategies with TLR antagonists is warranted. [source] Granulomas in common variable immunodeficiency: A diagnostic dilemmaAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2004Karyn R Lun SUMMARY A 60-year-old man with common variable immunodeficiency presented with a 7-year history of violaceous plaques and papules on the thighs, arms and trunk. In the preceding 2 years he had developed new lesions on both hands. He had been previously diagnosed with sarcoidosis on the basis of skin and visceral histology, but subsequent opinion was that these were sarcoid-like granulomas rather than being representative of true sarcoidosis. Biopsy of the hand lesions showed necrotizing granulomas, and a single acid-fast bacillus (AFB) was identified on Wade,Fite stain. Subsequent repeat tissue biopsies for histology, culture and polymerase chain reaction testing failed to confirm the presence of mycobacterial organisms and it was felt that the organism was a contaminant introduced during tissue processing. The hand lesions responded well to intralesional injections of triamcinolone acetonide 10 mg/mL and oral tetracycline 500 mg b.d. was later introduced with a good clinical response. The diagnostic dilemma of finding granulomatous inflammation in a patient with common variable immunodeficiency, and the significance of a single AFB on histology are discussed. The treatment of sarcoid-like granulomas with tetracycline therapy is also commented on. [source] Decrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiencyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009J. Horn Summary Common variable immunodeficiencies (CVID) are a heterogeneous group of antibody deficiency disorders complicated by autoimmune, lymphoproliferative and/or granulomatous manifestations, suggesting variations in immunoregulation. We sought to quantify regulatory CD4 T cells (Treg cells) in the blood of CVID patients and to correlate the frequency with clinical manifestations and classification subgroups. Blood samples from 99 CVID patients in Freiburg, London and Sydney, who had been phenotyped clinically and stratified according to their memory B cell phenotype (Freiburg and Paris classification schemes), were analysed for the proportion of Treg cells, defined either as CD25+/forkhead box P3 (FoxP3)+, CD25+/CD127low/FoxP3+ or CD25+/CD127low CD4+ T cells, and results compared with 49 healthy controls. Irrespective of the phenotype used to define them, there was a significant decrease in the Treg cell proportion in patients with granulomatous disease and immune cytopenias. This allowed the definition of a subgroup of CVID patients with abnormally low Treg cells, which had a higher rate of these two manifestations as well as autoimmune disease in general. There was also a significant reduction in the proportion of Treg cells in the Freiburg group Ia compared with other CVID patients and controls, but there were no differences between the Paris groups. The reduction in Treg cells in subsets of CVID patients may be relevant to their clinical manifestations, and may contribute to our understanding of the pathogenesis of CVID complications. [source] Some cases of common variable immunodeficiency may be due to a mutation in the SBDS gene of Shwachman,Diamond syndromeCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008S. Khan Summary Known genetic defects currently account for only a small proportion of patients meeting criteria for ,probable' or ,possible' common variable immunodeficiency (CVID). A 59-year-old male with a 12-year history of CVID on intravenous immunoglobulin (IVIG) is presented who developed bronchiectasis, cytopenias and malabsorption that are recognized complications of CVID. Work-up for his malabsorption suggested the possibility of Shwachman,Diamond syndrome, confirmed by mutation testing. With the identification of the molecular defect in Shwachman,Diamond syndrome (SDS), it is becoming clear that not all SDS patients have the prominent features of neutropenia or pancreatic malabsorption. A meta-analysis of published immunological defects in SDS suggests that four of 14 hypogammaglobulinaemic SDS patients meet criteria for ,possible' CVID. Mutations in the SBDS gene may therefore be the fifth identified molecular defect in CVID. [source] Translational Mini-Review Series on Immunodeficiency: Molecular defects in common variable immunodeficiencyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. Bacchelli Summary Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10,15% of all cases of CVID and it is highly likely that further genetic defects will be identified. [source] Measurement of peripheral B cell subpopulations in common variable immunodeficiency (CVID) using a whole blood methodCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005B. L. Ferry Summary Recent reports have described reduced populations of CD27+ memory B cells and increased percentages of undifferentiated B cells in peripheral blood of patients with common variable immunodeficiency (CVID). This work has prompted two attempts to classify CVID based on rapid flow cytometric quantification of peripheral blood memory B cells and immature B cells. Evidence to support the hypothesis that such in vitro B cell classification systems correlate with clinical subtypes of CVID is being sought. For the classification to be useful in routine diagnosis, it is important that the flow cytometric method can be used without prior separation of peripheral blood mononuclear cells (PBMC). We have examined 23 CVID patients and 24 controls, using both PBMC and whole blood, and find an excellent correlation between these methods. The reproducibility of the method was excellent. We classified the CVID patients by all three of the existing classifications, including secretion of immunoglobulin by B cells in vitro as described by Bryant, as well as the more recent flow cytometric classification methods. Only one patient changed classification as a result of using whole blood. [source] Prevalence of SAP gene defects in male patients diagnosed with common variable immunodeficiencyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2004D. EASTWOOD SUMMARY The molecular basis of common variable immunodeficiency (CVID) is undefined, and diagnosis requires exclusion of other diseases including X-linked lymphoproliferative disease (XLP). This rare disorder of immunedysregulation presents typically after Epstein,Barr virus infection and results from defects in the SAP (SLAM associated protein) gene. SAP mutations have been found in a few patients diagnosed previously as CVID, suggesting that XLP may mimic CVID, but no large-scale analysis of CVID patients has been undertaken. We therefore analysed 60 male CVID and hypogammaglobulinaemic patients for abnormalities in SAP protein expression and for mutations in the SAP gene. In this study only one individual, who was found later to have an X-linked family history, was found to have a genomic mutation leading to abnormal SAP cDNA and protein expression. These results demonstrate that SAP defects are rarely observed in CVID patients. We suggest that routine screening of SAP may only be necessary in patients with other suggestive clinical features. [source] | ||||||||||||||||||||||