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Results for “Common Variable Immunodeficiency”

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PubMed2005

Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients.

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by defective Ab production and recurrent bacterial infections. The largely unknown causes are likely to comprise a diverse set of genetic or acquired defects. In this study, we investigated terminal B cell differentiation in lymph nodes from CVID patients. Up to the germinal center B cell stage, B cell differentiation was normal but terminal plasma cell development was found to be impaired. Using differential Blimp-1 and Syndecan-1 expression in controls, we defined three different plasma cell subsets that correspond to progressive developmental stages locating to different sites in the lymph node. In the CVID patients, we could only detect one or two of these subsets indicating a defective differentiation. Thus, terminal plasma cell differentiation was found to be impaired despite normal expression of Blimp-1. B cells reaching only the first stage of plasma cell differentiation were further unable to undergo isotype switching and to up-regulate activation markers on B cells stimulated in vitro.

Adult↗

PubMed2005

Severe hypoleptinaemia associated with insulin resistance in patients with common variable immunodeficiency.

OBJECTIVE: Common variable immunodeficiency (CVI) is a primary immunodeficiency syndrome characterized by impaired production of antibodies and recurrent infections. Delay in diagnosis leads to metabolic wastage and low body weight. Leptin, a hormone produced by white adipose tissue, modulates insulin action by signal transduction cross-talk and by direct action on pancreatic beta-cells. We hypothesized that patients with CVI might present a defective regulation of leptin production and insulin resistance. PATIENTS: Thirteen CVI patients (39 +/- 11 years) under gammaglobulin replacement were evaluated in parallel with 13 gender-, age-, body weight- and body mass index (BMI)-matched healthy voluntaries, and with data from two large population series, the Bruneck and the Hoorn Studies. MEASUREMENTS: Serum leptin and insulin levels, homeostasis model assessment - insulin resistance (HOMA-IR), body composition, haematological, biochemical and immunoglobulin measurements were obtained. Data were analysed by a one-way analysis of variance (anova) and by Pearson's rank analysis. The institutional ethics committee approved the study, and informed consent was obtained from patients and controls. RESULTS: No differences were found between CVI and the control group when comparing gender distribution, age, body weight, BMI, waist/hip ratio, relative body fat and fasting glucose levels. Leptin levels were lower (P < 0.05) in CVI patients than in controls and lower than fasting leptin levels detected in a large population study. CVI patients' serum leptin levels did not correlate with BMI (r = 0.074, P = 0.8) and their high HOMA-IR indicated insulin resistance. CONCLUSIONS: CVI patients are relatively hypoleptinaemic and insulin resistant, and their serum leptin levels are not correlated to their BMI.

Adult↗

PubMed2002

Panhypopituitarism in a child with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) represents a group of heterogeneous, still undifferentiated, syndromes that are all characterized by defective antibody formation. It is often associated with autoimmune disease. METHODS: An African-American girl was diagnosed with CVID at age 3 years. She was seen during an adrenal crisis precipitated by pneumonia at the age of 8 years and 10 months. The diagnosis of panhypopituitarism was established soon after. RESULTS: Panhypopituitarism in this patient was believed to be the result of the autoimmune process known as lymphocytic hypophysitis. This hypothesis was suggested by the results of magnetic resonance imaging. CONCLUSIONS: Awareness of the possibility of this process in children or adults with CVID may lead to earlier diagnosis of panhypopituitarism. These patients also have failure to thrive, and earlier diagnosis may avoid a life-threatening event.

Autoimmune Diseases↗

PubMed2003

Antibody response in common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) describes a heterogeneous group of immunologic disorders of unknown etiology. It is characterized by low levels of serum immunoglobulin (Ig) and impaired antibody response. OBJECTIVE: To describe antibody response and the kinetics of IgG decline in patients identified with CVID. METHODS: Clinical and immunologic observations of four patients identified with CVID were obtained by chart review. RESULTS: Antibody response to polysaccharide antigens in patients identified with CVID is lost earlier than the antibody response to protein antigens, which may be preserved even in the face of profound hypogammaglobulinemia. In three patients who were followed prospectively, the Ig loss was progressive. CONCLUSIONS: Absence of antibody response to polysaccharide antigens may be a universal finding in patients with CVID, whereas preservation of T cell-dependent protein antibody response may be seen.

Adolescent↗

PubMed2006

Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients.

Common variable immunodeficiency disease (CVID) is a primary immune disorder affecting B cells and characterized by hypogammaglobulinemia and recurrent infections. To elucidate the clinical and immunological heterogeneity of this condition, we have studied B and T cell subsets in 25 CVID patients. In eleven of them, we observed a remarkable relative expansion of a B cell subpopulation (CD19(hi)/CD21(lo) cells) characterized by the absence of CD23 and the reduced expression of the chemokine receptors CXCR5 and CCR7. Our analyses demonstrated in these patients that the expansion of CD19(hi)/CD21(lo) cells correlates with a selective decrease of circulating naïve and CD21(hi) memory B lymphocytes. The same group of patients displayed a simultaneous severe reduction of naïve CD4+ T cells associated with decreased levels of T cell receptor excision circles. These observations suggest that a combined defect in generation of B and T subpopulations may account for the abnormal immunophenotype characterizing this subgroup of CVID patients.

Adolescent↗

PubMed2000

Impaired up-regulation of CD86 in B cells of "type A" common variable immunodeficiency patients.

Common variable immunodeficiency (CVID) is characterized by defective B cell maturation and antibody formation resulting in low serum antibody levels of most or all Ig isotypes. A specific subgroup of patients ("type A") has normal numbers of mature surface (s)IgM / sIgD- positive circulating B cells. However, since these lymphocytes do not respond to in vitro stimulation by differentiation and Ig synthesis, they seem to suffer from so far unknown intrinsic defects. Analyzing the expression pattern of a large set of B cell activation-specific surface markers, we found that type A CVID patients show a highly reduced expression of the CD28 / CTLA-4 ligand CD86 (B7-2) and of the lymphocyte activation marker CDw137 when compared to B cells of healthy donors and non-type-A CVID patients. The lowered CD86 expression levels were found to correlate with reduced levels of CD86 mRNA. Since combined stimulation via B cell antigen receptor and CD40 cross-linking did not rescue the defects in CD86 and CDw137 expression, B cells of CVID type A patients resemble functionally unresponsive lymphocytes incapable of cooperating with T cells. The fact that these cells accumulate in type A CVID patients suggests a causal relationship with the pathogenesis of this disease.

Adult↗

PubMed2006

Costimulatory molecules and cytokine production by T lymphocytes in common variable immunodeficiency disease.

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by hypogammaglobulinaemia and recurrent infections. Although early works pointed to a primary B-lymphocyte defect as a cause of the disease, a failure in T-lymphocyte cooperation has also been suggested. T cells exert their costimulatory function through either membrane costimulatory molecules or secreted cytokines, both having an influence in the development of the humoral response. The aim of our study was to evaluate whether an abnormal expression and induction of costimulatory molecules or alterations in the production of cytokines by T cells cause deficient T/B cooperation in CVID patients. We studied the expression and upregulation of costimulatory molecules (CD28, CD40L/CD154 and CTLA-4/CD152) and production of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) in purified T lymphocytes from CVID patients stimulated with optimal doses of anti-CD3 or suboptimal doses of anti-CD3 and anti-CD28. Stimulated T cells from CVID patients expressed normal levels of CD28, CD40L/CD154 and CTLA-4/CD152 when compared with controls. Except for higher production of IL-4 after stimulation with anti-CD3, T cells of CVID patients produced similar amounts of cytokines compared with controls. An imbalance between costimulatory molecules expression (CD28, CD40L/CD154 and CTLA-4/CD152) and cytokine production by T cells does not explain a deficient cooperation between T and B cells in this group of CVID patients.

Adult↗

PubMed2002

Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune disorder characterized by antibody deficiency and a decrease in serum IgG and IgA, IgM, or both levels at least 2 SDs below the mean for age and not attributed to other known immunologic disorders. These patients often present with frequent and severe episodes of pneumonia before diagnosis. The standard treatment, intravenous immunoglobulin (IVIG), has been available for the past 20 years. No large-scale study has compared the incidence of pneumonia in these patients before and after IVIG treatment. OBJECTIVE: The aim of this study was to document the effectiveness of intravenous immunoglobulin treatment on the incidence of pneumonia in patients with CVID. METHODS: We performed chart reviews and interviews of patients with laboratory-confirmed CVID seen at our clinical center. The number of episodes of pneumonia was documented before and after treatment with immunoglobulin replacement therapy. RESULTS: The histories of 50 patients were reviewed (mean current age, 42 +/- 16.3 years; age range, 10-78 years; 20 male and 30 female patients). Forty-two (84%) of the 50 patients with CVID had pneumonia at least once before receiving immunoglobulin treatment, and 11 of 42 of these patients had multiple episodes. After treatment with gamma globulin over a mean period of 6.6 +/- 5.2 years (range, <1-20 years), the number of patients experiencing pneumonia significantly decreased to 11 (22%) of 50. In most cases these patients had pneumonia in the first year of immunoglobulin treatment. CONCLUSION: The treatment of CVID with IVIG significantly reduces the incidence of pneumonia.

Adolescent↗

PubMed1999

Gastric pathology in patients with common variable immunodeficiency.

BACKGROUND/AIMS: Common variable immunodeficiency (CVID) is an immunological disorder characterised by defective antibody production. Patients with CVID have a high risk of gastric cancer. It has been suggested that gastric cancer results from an interaction between environmental factors and a genetic predisposition. The role of Helicobacter pylori as an environmental factor in gastric carcinogenesis is of current interest. Moreover, p53 gene mutations have been reported in gastric cancer. This study focuses on the gastric pathology of patients with CVID and correlation with H pylori infection. METHODS: Thirty four consecutive dyspeptic patients with CVID (mean age 49.6 years, range 14-72; 17 men) were included in the study. An upper gastrointestinal endoscopy was performed and biopsy specimens were taken from the antrum, incisura angularis, and gastric body. Biopsies were used for histological assessment, to identify the presence of H pylori, and to evaluate p53 overexpression. RESULTS: H pylori infection was detected in 14/34 (41%) patients. Chronic active gastritis involving both antrum and body was observed more frequently in H pylori positive (79%) than H pylori negative (20%) patients (p = 0.001). Similarly, a histological feature of multifocal atrophic gastritis was found more frequently in infected (50%) than uninfected patients (10%) (p = 0.012). In addition, one case of gastric adenocarcinoma and another of notable dysplasia were observed in the H pylori positive group. Overexpression of p53 was found in six (18%) patients, including one with normal gastric mucosa. CONCLUSIONS: It can be hypothesised that both H pylori and p53 alterations play a role in the gastric carcinogenesis of patients with CVID.

Adolescent↗

PubMed2006

Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients.

Common variable immunodeficiency (CVID) is primary hypogammaglobulinaemia with an unknown aetiopathogenesis. Although various abnormalities of T and B cells have been described, their pathogenetic roles are unclear. We determined T and B lymphocyte subsets known to be abnormal in CVID in order to disclose possible relations between numerical abnormalities in those cells. Markers associated with B cell development (CD21, CD27, IgM, IgD) were determined on B lymphocytes (CD19+); T lymphocyte development (CD45RA, CD45RO, CD62L) and activation markers (CD25, CD27, CD28, CD29, CD38, CD57, HLA-DR) were determined on CD4+ and CD8+ T lymphocytes in 42 CVID patients and in 33 healthy controls. Abnormalities in CD4+ T lymphocyte activation markers (increase in CD29, HLA-DR, CD45RO, decrease in CD27, CD62L, CD45RA) were observed particularly in patients with a decreased number of memory (CD27+) and mature (CD21+) B cells (group Ia according to the Freiburg group's classification), while abnormalities observed in CD8+ cells (increase in CD27 and CD28 and decrease in HLA-DR, CD57 and CD38) did not depend upon grouping patients together according to B lymphocyte developmental subpopulations. We observed correlations between immature B cells (IgM+ CD21-) and expression of CD27, CD62L, CD45RA, CD45RO and HLA-DR on CD4+ T cells in CVID patients but not in the control group. The expression of CD27 and CD45RA on CD4+ T lymphocytes, such as the percentage of IgD+ CD27- and IgD+ CD27+ cells in B lymphocytes, showed age dependency to be more significant than in the control group. Our study demonstrates that T and B lymphocyte abnormalities in CVID are partially related to each other. Some of those abnormalities are not definite, but may evolve with age of the patient.

Adult↗

PubMed2002

Characterization of Herpesvirus saimiri-transformed T lymphocytes from common variable immunodeficiency patients.

Common variable immunodeficiency (CVID) is a very frequent but heterogeneous syndrome of antibody formation. The primary defect remains unknown, but many reports describe peripheral blood T lymphocyte dysfunctions in a substantial proportion of CVID patients, which may impair T--B cell collaboration. In order to investigate whether such putative defects were intrinsic to T cells or, rather, secondary to quantitative differences in T cell subset distribution, or to other described disorders, we have used Herpesvirus saimiri (HVS) for the targeted transformation of CVID CD4+ and CD8+ T cells and subsequent functional evaluation by flow cytometry of their capacity to generate cell surface (CD154, CD69) or soluble (IL-2, TNF-alpha, IFN-gamma) help after CD3 engagement. Unexpectedly, the results showed that 40 different CVID blood samples exposed to HVS gave rise with a significantly increased frequency to transformed CD4+ T cell lines, compared to 40 age-matched controls (27% versus 3%, P < or = 0.00002) suggesting the existence of a CVID-specific signalling difference which affects CD4+ cell transformation efficiency. The functional analysis of 10 CD4+ and 15 CD8+ pure transformed T cell lines from CVID patients did not reveal any statistically significant difference as compared to controls. However, half of the CD4+ transformed cell lines showed CD154 (but not CD69) induction (mean value of 46.8%) under the lower limit of the normal controls (mean value of 82.4%, P < or = 0.0001). Exactly the same five cell lines showed, in addition, a significantly low induction of IL-2 (P < or = 0.04), but not of TNF-alpha or IFN-gamma. None of these differences were observed in the remaining CD4+ cell lines or in any of the transformed CD8+ cell lines. We conclude that certain CVID patients show selective and intrinsic impairments for the generation of cell surface and soluble help by CD4+ T cells, which may be relevant for B lymphocyte function. The transformed T cell lines will be useful to establish the biochemical mechanisms responsible for the described impairments.

Adolescent↗

PubMed2006

[Health care and infective aspects in patients affected by common variable immunodeficiency assisted in the Lazio Regional Authority Reference Centre for Primary Immunodeficiencies].

Common variable immunodeficiency (CVID) is a chronic condition characterised by a predominant defect of humoral immunity. In most cases the diagnosis of CVID is made during adulthood; the main clinical features of CVID are chronic and relapsing infections (mainly of respiratory and gastroenteric tracts). CVID patients may also develop neoplastic and autoimmune diseases. In our centre (the Regional Centre for Primary Immunodeficiencies of the Lazio Regional Authority) we administered a 23-item questionnaire to 60 patients with CVID undergoing substitutive therapy with intravenous immunoglobulins (IVIG) about their demographic characteristics, time of clinical onset, time of diagnosis of CVID, clinical features, IVIG doses and administration intervals, and self-assessment of health status. In addition, the clinical history of all patients was reviewed, and the levels of serum IgG, IgA and IgM were evaluated and compared with the pre-therapy serum concentration. Moreover, an analysis of the treatment costs was performed. At onset, 67.2% of patients presented recurrent respiratory infections, and 50% had infections of the lower respiratory tract; 39.6% of the patients had gastroenteric infections. Most patients (57%) had recurrent infections of at least 2 of the respiratory, gastroenteric and/or urogenital tracts. In 37.9% of the group the diagnosis of CVID was made in less than 2 years after the beginning of symptoms, but in many cases (22.4%) the diagnosis took more than 10 years. 93% of patients are treated with a dose of IVIG between 6 and 15 g per administration, with intervals between 2 and 3 weeks. The review of patients'clinical history showed that 43% of patients have had respiratory infections during the follow-up in our Centre, 43% have splenomegaly (3% were also subjected to splenectomy) and 18.3% have autoimmune diseases. The mean concentration of IgG before the beginning of IVIG therapy was 235 mg/dl, while during the follow-up it was 664 mg/dl. Given the long time often required for diagnosis, general physicians and specialists should be better informed in order to make diagnosis swifter. The substitutive therapy with IVIG is effective in preventing recurrent infections and complications. A thorough follow-up is important for diagnosing neoplastic and autoimmune complications; in addition, immunologic analysis of peripheral blood and bone marrow are useful in identifying subgroups of patients with more severe clinical features. Finally, in selected patients, treatment costs may be controlled by modifying the dosage of IVIG or the intervals between administrations.

Adolescent↗

PubMed1991

Expression of immunoglobulin genes in common variable immunodeficiency.

Five common variable immunodeficiency (CVI) patients were analyzed for expression of immunoglobulin (Ig) genes. In the pokeweed mitogen (PWM)-induced Ig-production assay, the combination of T and B cells showed that all patients' T cells had normal helper functions and all patients' B cells had profound defects. The defective B-cell maturation stages based on their Ig gene expression patterns were variable. One of five patients showed normal mu-chain gene expression and nearly normal IgM production, but neither IgG nor IgA production, which suggested that this patient's B-cell defects might lie on a mu- to gamma or mu- to alpha class-switch stage. B cells in another patient showed low mu-chain gene expression and low IgM production, but an Ig enhancer region, which is an important region for expression of Ig genes, was intact. Thus, this patient might have a transacting factor defect which interacts with the Ig enhancer region. The other three patients showed no mu-chain gene expression and no IgM production. Thus, their B-cell defects lay on the B-cell maturation stage, similar to X-linked agammaglobulinemia. These results showed that primary B-cell defects in CVI occurred at several B-cell differentiation stages, which could be recognized by expression of Ig genes.

Adult↗

PubMed1992

[Common variable immunodeficiency and sarcoidosis].

Variable Common Immunodeficiency (VCI) can course with non necrotizing epithelioid granulomatosis of sarcoid type. Although this entity is frequently referred, it is rare and its significance is not clear. The immunological study and response to treatment with corticoids and i.v. immunoglobulins of a patient is who suffered VIC with sarcoid granulomas on lymph node, liver and skin biopsies is here presented. The association between VCI and granulomatosis is discussed.

Adult↗

PubMed2000

[CVID (common variable immunodeficiency): heterogeneous clinical manifestation of the commonest symptomatic primary immunodeficiency disease].

Common variable immunodeficiency is the most common symptomatic primary immunodeficiency disease. The patients typically present with a long history of respiratory tract infections, sometimes sarcoid-like lesions and in rare cases boils. Heterogeneity of initial clinical manifestations as well as insufficient knowledge of the syndrome often delay the diagnosis. However, early therapy is important to reduce infections and in particular the development of bronchiectasis. Documenting 19 cases, we discuss initial clinical manifestations, some clinical complications, diagnostic procedures and therapeutic management.

Adolescent↗

PubMed2001

Long term recovery of IgG and IgM production during HIV infection in a patient with common variable immunodeficiency (CVID).

AIMS: Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency. This paper describes the immunological consequences of human immunodeficiency virus (HIV) infection in a patient with familial CVID subsequently treated with highly active antiretroviral therapy (HAART). METHODS: Serial measurements over 11 years of serum immunoglobulins, specific antibodies to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and HIV viral load were made. RESULTS: The patient recovered total serum IgG and IgM, but not IgA production, with adequate concentrations of specific antibodies, allowing withdrawal of intravenous immunoglobulin without an increase in infections. T cell numbers gradually declined and the patient developed a high grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral load fell from 472 000 to < 50 copies/ml, and CD4+ T cell numbers increased from 13 to 661 x 10(6)/litre. Antibody production was maintained after suppression of viral load. CONCLUSIONS: This is the first definitive report of reversal of IgG and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA supports the concept of separate predisposing genetic factors for selective IgA deficiency, which when combined with others lead to CVID. Furthermore, a persistently high viraemia is not required to maintain the recovery of immunoglobulin values, suggesting this depends either on a transitory effect of a high viral load, or a persistence of low amounts of virus.

Adult↗

PubMed2000

Noncaseating granulomatous disease in common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) are occasionally recognized to have a concurrent noncaseating granulomatous disease. The granulomatous disease (GD) associated with CVID shares many clinical properties typical of sarcoidosis. Some investigators speculate that the GD-CVID is actually sarcoidosis that is expressed atypically because of the patient's immunodeficiency. Clinical differences, however, have led other investigators to speculate that the GD-CVID is a distinct "sarcoid-like" granulomatous process.

Aged↗

PubMed2004

Common variable immunodeficiency: a review.

Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody deficiency syndrome. The predominant manifestation is hypogammaglobulinemia. CVID is characterized by recurrent bacterial infections, especially of the upper and lower respiratory airways, and is also associated with an increased incidence of autoimmune and neoplastic disorders. Most patients are diagnosed as adults and delay in the recognition of the disease is common. Several T and B cell defects have been described, although the underlying cause is still unknown.

Common Variable Immunodeficiency↗