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Results for “Common Variable Immunodeficiency”

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PubMed1997

Uncoupling of T-cell antigen receptor and downstream protein tyrosine kinases in common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and the underlying mechanisms leading to the immunodeficiency. Although the overt defect is an impairment in B-cell function, there is increasing evidence of primary T-cell dysfunctions in a proportion of patients with CVID. We have analyzed T-cells from six CVID patients for activation of both early and late events in response to TCR triggering. The data showed that T-cells from three of six CVID patients were defective in the capacity to initiate the TCR/CD3 signaling pathway by activating intracellular tyrosine kinases, associated with impaired proliferative responses to TCR/CD3 triggering. Since both surface expression of the TCR/CD3 complex and intracellular expression of key tyrosine kinases such as p56lek and ZAP-70 were normal in these patients, our data suggest a defect in the earliest step of TCR signal transduction.

Adult↗

PubMed1993

Defective interleukin-2 and interferon-gamma gene expression in response to antigen in a subgroup of patients with common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and in the underlying mechanisms leading to the immunodeficiency. The impairment of B-cell function can be due to an intrinsic defect of the B cells, a deficiency in the function of the antigen-presenting cell, or a dysfunction in the course of T-cell activation. In the present report we have focused our attention on T-lymphocyte activation in three patients with CVID. Numbers of T and B cells, as well as CD4 and CD8 T cell subsets, were within the normal range. The patients' B cells secreted IgM but did not secrete IgG and IgA in response to B-cell stimuli in vitro. Addition of allogeneic T cells was followed by an increase in IgM production but had no effect on the other immunoglobulin isotypes. Examination of T-cell function revealed impaired proliferative response, interleukin-2 (IL-2) and interferon-gamma gene expression and IL-2 release after antigenic stimulation, whereas T-cell proliferation, as well as IL-2 gene expression and release in response to stimulation via anti-CD3, were comparable to those of healthy control subjects. Anti-CD3-induced IFN-gamma gene activation in T cells from two patients was comparable to that of control subjects, whereas T cells from the third patient showed reduced expression of IFN-gamma mRNA. In contrast to the decreased IL-2 and IFN-gamma mRNA levels, IL-2R transcripts examined in parallel were normal in CVID T cells on stimulation with antigen. The defect in IL-2 and IFN-gamma mRNA expression after stimulation with antigen, but not with anti-CD3, suggests an abnormality confined to T-cell activation by the T-cell receptor.

Adult↗

PubMed1993

Defective calcium-dependent signal transduction in B lymphocytes of a certain common variable immunodeficiency.

Two different common variable immunodeficiency patients were studied. Patient 1 showed hypogammaglobulinemia in all major classes of gammaglobulins and slightly reduced percentages of circulating CD19+ cells, CD20+ cells and surface IgG-or IgA-bearing cells with a normal percentage of surface IgM-bearing cells. Patient 2 showed normal levels in IgM with IgG and IgA deficiencies and almost normal percentages of circulating CD19+ cells, CD20+ cells and surface IgM-, IgG- or IgA-bearing cells. The proliferative responses of peripheral blood mononuclear cells to B cell mitogen, Staphylococcus aureus Cowan I, were reduced in patient 1 but not in patient 2. The intracellular calcium concentrations in lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus from patient 2 were increased after anti-mu stimulation. The concentrations were scarcely increased in LCLs from patient 1. These results suggest that B cells of patient 1 have a defective Ca(2+)-dependent signal transduction pathway, resulting in a failure of cell activation and cell proliferation. The defect in B cells of patient 2 may exist on immunoglobulin gene switching or expression rather than the Ca(2+)-dependent signal transduction pathway.

Agammaglobulinemia↗

PubMed2003

Duodenal pathology and clinical-immunological implications in common variable immunodeficiency patients.

OBJECTIVES: Common variable immunodeficiency (CVID) is an immunological disorder characterized by defective antibody production. An increased prevalence of celiac disease has been suggested in patients with this disorder. This study aimed to assess duodenal pathology and its clinical implications in these patients. METHODS: A total of 32 consecutive CVID patients with anemia or GI symptoms were enrolled. Patients underwent upper endoscopy, and biopsy specimens were taken in the descending duodenum for histological assessment. A blood sample was obtained to determine immunoglobulin and Hb levels and to evaluate the CD4+ T-lymphocyte count. Body mass index was calculated for all patients. RESULTS: Histological assessment of duodenal specimens revealed the presence of villous atrophy in 10 (31.2%) patients, a feature of nodular lymphoid hyperplasia in five (15.6%), and mild duodenitis in two (6.3%), whereas normal histology was observed in the remaining 15 (46.9%) patients. Patients with villous atrophy had anemia more frequently than those without, whereas the frequency of persistent diarrhea did not differ between these two groups. Moreover, both CD4 levels and body mass index were significantly lower in patients with atrophy than in controls. CONCLUSIONS: Duodenal villous atrophy is very frequent in symptomatic CVID patients, with relevant clinical and immunological implications. Specifically, this histological alteration is significantly associated with anemia, malnutrition, and low blood CD4+ lymphocyte levels.

Common Variable Immunodeficiency↗

PubMed2006

Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency.

BACKGROUND & AIMS: Common variable immunodeficiency (CVID) patients can develop an idiopathic inflammatory bowel disease resulting in chronic diarrhea and life-threatening malabsorption. This study was designed to assess the status of the gastrointestinal tract and to define the mucosal immune abnormalities in patients with and without symptomatic gut inflammatory disease. METHODS: CVID patients underwent tests of gut absorption, peripheral blood mononuclear cell phenotyping, and upper and lower endoscopy for histology and lamina propria mononuclear cell (LPMC) cytokine production. RESULTS: CVID patients with gastrointestinal symptoms differed from asymptomatic CVID patients by having significantly longer duration of disease and lower body mass index, D-xylose absorption, serum albumin, CD4/CD45RA cells, CD3/CD25 cells, and natural killer cells. Symptomatic CVID patients showed diffuse histologic inflammatory changes in the duodenal and colonic mucosa including villus blunting, increased lamina propria and intraepithelial lymphocytes, and epithelial apoptosis, less frequently seen in asymptomatic patients. LPMCs from symptomatic CVID patients produced significantly higher T-helper (Th) 1 cytokines, interleukin-12, and interferon-gamma. Compared with the Th1 cytokines produced by LPMCs from Crohn's disease, CVID patients did not produce excess amounts of interleukin-23, interleukin-17, or tumor necrosis factor-alpha. CONCLUSIONS: The idiopathic inflammatory bowel disease associated with gastrointestinal symptoms in CVID is a unique combination of diverse histologic findings accompanied by excessive Th1 cytokine production, distinct from that in Crohn's disease. These data show that human gut mucosal inflammatory disease can occur with excess interleukin-12 and interferon-gamma production alone and provide a rationale for developing targeted therapies for this complication of CVID.

Adult↗

PubMed1992

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.

Antibody Formation↗

PubMedDate not supplied

Evaluation of some immune functions in a patient affected by common variable immunodeficiency using luminescent techniques.

Common variable immunodeficiency is a primary immunodeficiency characterized by a failure of antibody synthesis, whose fundamental immunologic abnormality is still unknown. In our study, we evaluated some immune functions using chemiluminescence in a 32-year-old woman affected by common variable immunodeficiency. In particular, we showed an impairment of her lymphomonocyte proliferative response which was evaluated using a method based on the bioluminescent measurement of ATP. Besides, we found a reduction of her lymphomonocyte IL2 and IL4 production: the IL4 production was evaluated through an ELISA method, whereas the IL2 activity was determined by its ability to support the IL2-dependent murine T-cell line (CTLL) proliferation which was established through a method based on the bioluminescent measurement of ATP. Finally, we evaluated both yeast-induced and fMLP-induced polymorphonuclear and monocyte oxidative metabolism through a luminol-amplified chemiluminescence; these functions were within normal values. Therefore, in our patient affected by common variable immunodeficiency, we demonstrated an impairment of cellular immunity, which might contribute to the pathogenesis of the disease.

Adenosine Triphosphate↗

PubMed2001

Clonal CD8 infiltration of the skin in common variable immunodeficiency: a prelymphomatous stage?

Common variable immunodeficiency is a heterogeneous syndrome characterized by hypogammaglobulinemia and recurrent bacterial infections. Patients with this syndrome also have an increased incidence of autoimmune disease and malignancy, most notably lymphoproliferative disorders. The treatment for common variable immunodeficiency is supported by the use of intravenous infusion of immunoglobulins that allows for control of the disease and avoidance of recurrent opportunistic infections. This report describes a young patient having common variable immunodeficiency who presented with a clonal CD8(+) lymphocytic infiltration of the skin clinically manifesting as a widespread papulonodular eruption and resolving with intravenous immunoglobulin therapy. We speculate that such a unique cutaneous presentation may represent a prelymphomatous condition because of the development of an autonomous T-suppressor/cytotoxic cell clone, possibly also responsible for the impaired immunoglobulin production.

Adult↗

PubMedDate not supplied

[About a case of common variable immunodeficiency--revision of hypogammaglobulinemias].

Common variable immunodeficiency is a primary immune deficiency characterized by heterogeneous immunologic disorders of unknown etiology. Its clinical manifestations include recurrent infections, autoimmune diseases, lymphoid hyperplasia, granulomatous diseases and malignancy. It can appear in patients with immunoglobulin A deficiency. The authors report the clinical case of a patient with common variable immunodeficiency and history of respiratory infections from the age of 9 months old, associated with the appearing of bronchiectasis.

Adult↗

PubMedDate not supplied

[Therapy with cytokines and thymic factors in a complicated case of common variable immunodeficiency].

A case with common variable immunodeficiency associated to hyperprolactinaemia and severe damage of mucosal defenses is reported, in which humoral and cellular response was widely explored. The impact of the cytokines therapy was analyzed as complementary schedule to the conventional therapy with gammaglobuline. Immune response to the treatment was long-time evaluated in relation with therapeutic interventions. Combination of alpha 2 b-IFN, thymic factors, gammaglobuline and GM-CSF was a good alternative to treat complicated common variable immunodeficiency.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Orthotopic liver transplantation for chronic hepatitis in two patients with common variable immunodeficiency.

Two patients with common variable immunodeficiency underwent orthotopic liver transplantation for chronic hepatitis, unequivocally caused by hepatitis C virus in one case. Although one patient had pneumonia 8 days after surgery and the other developed hepatic venular stenosis in the transplanted liver, both had a reasonably good quality of life for at least 15 months. However, both subsequently died of recurrent hepatitis C virus hepatitis or hemorrhage after splenectomy for hypersplenism. This shows that severe infection is not a major problem in patients with common variable immunodeficiency after liver transplantation provided they undergo prophylactic antimicrobial and immunoglobulin therapy. The longer term prognosis must be regarded as poor until more data are available following transplantation in similar patients.

Adolescent↗

PubMed2005

Hypercalcemia in a patient with common variable immunodeficiency and renal granulomas.

Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. A granulomatous form of the condition is recognized. Renal involvement is rare. The authors present the first case of CVID with biopsy-proven noncaseating renal granulomas, in association with hypercalcemia. The mechanism of hypercalcemia in granulomatous disorders, and the difficulty of differentiating granulomatous CVID from sarcoidosis, are discussed.

Common Variable Immunodeficiency↗

PubMed1994

Common variable immunodeficiency: diagnosis and management.

OBJECTIVE: Common variable immunodeficiency is a heterogeneous syndrome characterized by humoral immunodeficiency, recurrent bacterial infections, and a variety of immunologic abnormalities. The goal of this article is to review the pathogenesis, clinical manifestations, diagnosis, and management of common variable immunodeficiency. DATA SOURCES: References are limited to the English language literature. Sources include computerized databases and bibliographies of recent articles and books. STUDY SELECTION: References that made important contributions to our understanding of the pathogenesis, clinical manifestations, diagnosis, and treatment of this disease were selected for inclusion in this review. RESULTS AND CONCLUSION: Common variable immunodeficiency is an idiopathic state of immune dysregulation that results in impaired antibody synthesis and the development of recurrent bacterial infections. This syndrome is also associated with a variety of autoimmune and neoplastic disorders. Effective management of these patients includes intravenous immunoglobulin replacement, vigorous treatment of infections, and readiness to promptly evaluate and treat unusual autoimmune and neoplastic complications should they appear.

Common Variable Immunodeficiency↗

PubMedDate not supplied

[Atypical presentation of common variable immunodeficiency without infections].

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immunodeficiency disease, the hallmark of which is hypogammaglobulinemia and poor specific antibody responses. Patients usually have recurrent bacterial infections, but there are a number of other comorbid disorders, including autoimmune disease and neoplasms. Most patients are diagnosed as adults, and delay in identifying the antibody defect is common. In the present report, we illustrate atypical initial presentation without infections in CVID. CLINICAL OBSERVATION: In 5 out of 30 patients with CVID (16.6 %) diagnosed in our hospital in the Autonomous Community of Madrid, the first manifestation of immunodeficiency was not an infection. Three patients presented with immune cytopenias (thrombocytopenic purpura [n = 2] and hemolytic anemia [n = 1]); one patient had pernicious anemia and one patient had insulin-dependent diabetes as the first clinical feature of CVID. Four patients had IgG levels below 400 mg/dl. CONCLUSIONS: Atypical presentations of CVID must be recognized to prevent delayed diagnosis. Presentation of CVID as an autoimmune disease in the absence of recurrent infections prompts us to suggest baseline testing of immunoglobulin levels in patients presenting with autoimmune disorders.

Adult↗

PubMed1993

Successful treatment of non-Hodgkin's lymphoma in a patient with common variable immunodeficiency.

A case of common variable immunodeficiency (CVID) who developed non-Hodgkin's lymphoma (NHL) of the rectum is reported. A 22-year-old male student in whom CVID was diagnosed at 7 years of age was referred to our department for the treatment of rectal NHL. The patient had stage IE disease confined to the rectum after clinical diagnostic procedures. He was initially treated with radiation therapy alone, but a relapse soon occurred in the paraaortic lymph nodes. He was successfully treated with CHOP-Bleo chemotherapy and supplementation with immunoglobulin preparations. He has since remained free of NHL and infectious complications for over 30 months despite his persistent immunodeficiency.

Adult↗

PubMed2002

A case of common variable immunodeficiency presenting with furunculosis.

Common variable immunodeficiency (CVID) is the most prevalent of the primary immunodeficiencies, and is characterised by low IgG and IgA, and sometimes IgM. There is some evidence of genetic susceptibility, with 20% of patients having a dominantly inherited disorder with variable expression. It is a heterogeneous disorder with protean manifestations, and as a result diagnosis is often delayed until the second or third decade, with resultant irreversible organ damage, in particular bronchiectasis. Effective treatment is available with regular 3-4-weekly infusions of immunoglobulin. The mechanism of the immunodeficiency has not yet been fully elucidated. The majority of patients present with recurrent sinopulmonary infection, however, this is a multisystem disorder and thus presents to physicians in diverse specialties including dermatology. Other clinical features of the disorder include gastrointestinal problems, granulomatous inflammation, cutaneous features, unusual presentations of enteroviral and mycoplasma infection, an increased incidence of autoimmunity, and a predisposition to lymphoma and stomach cancer. Therefore a knowledge of the disorder and appropriate suspicion by all clinicians of the possibility of such rare problems and a consequent low threshold for performing relevant investigations is imperative in allowing early recognition and instituting effective treatment. We describe a case of CVID identified when the patient developed widespread skin infection, fever and malaise. This case is an important example of a possible presentation of CVID within the dermatology clinic and demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of the rare primary immunodeficiencies.

Adult↗

PubMed2006

Polyclonal expansion of large granular lymphocytes in common variable immunodeficiency - association with neutropenia.

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency disease, characterized by low levels of circulating immunoglobulins and recurrent bacterial infections, particularly of the respiratory tract. T cell dysfunction is often present, and lymphoproliferative and autoimmune disorders as well as haematological cytopenias are frequently observed. In this study, we report a polyclonal expansion of large granular lymphocytes (LGL) in a substantial proportion of CVID patients, associated with splenomegaly, increased numbers of CD8(+) T cells, inverted CD4 : CD8 T cell ratios and neutropenia. CVID patients who had both increased numbers of LGL and granulocytopenia had elevated levels of soluble Fas ligand (sFasL). Our observations indicate that CVID may be added to the list of inflammatory diseases associated with increased numbers of LGL. Furthermore, our findings suggest common pathogenic mechanisms of granulocytopenia in CVID and lymphoproliferative disease of granular lymphocytes.

Adult↗

PubMed2006

TACI mutation in common variable immunodeficiency and IgA deficiency.

Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disease. Immunoglobulin A deficiency (IGAD) shares some clinical, laboratory, and genetic features with CVID and occurs with relatively greater frequency in first-degree relatives of individuals with CVID. Recently, patients with CVID and IGAD have been found to have mutations of the gene TNFRSF13B encoding the TACI (transmembrane activator and calcium-modulator and cyclophilin-ligand interactor), a member of the tumor necrosis factor-receptor superfamily. In this article, we review the various TACI mutations that have been identified so far. Although six mutations have been reported, no clear genotype-phenotype association has been shown to date. This suggests that the phenotypic expression of TACI mutation is affected by additional genetic and environmental factors. Analysis of a larger sample of patients will be needed to determine if the specific mutations are associated with a particular phenotype or predisposition to the common features of CVID and IGAD: autoimmunity, lymphoproliferation, or malignancy.

Animals↗