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Results for “Common Variable Immunodeficiency”

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PubMed2002

Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease.

Hypogammaglobulinemia is the hallmark of common variable immunodeficiency (CVID) syndrome, a heterogeneous disorder predisposing patients to recurrent bacterial infections. In this study, we investigated the peripheral B-cell compartment of 30 well-characterized CVID patients in comparison to 22 healthy controls. Flow cytometric analysis of peripheral blood lymphocytes revealed a reduction of class-switched CD27(+)IgM(-)IgD(-) memory B cells below 0.4% in 77% of our patients (group I), while this B-cell subpopulation exceeded 0.5% in all healthy donors and in 23% of CVID patients (group II). These results correlate well with the capacity of peripheral blood lymphocytes to produce immunoglobulins in vitro upon stimulation with Staphylococcus aureus Cowan I (SAC) plus interleukin-2 because the production of immunoglobulin G in vitro is entirely dependent on the presence of switched memory B cells. The subdivision of group I into patients with an increased proportion of CD21(-) peripheral B cells (> 20%; group Ia) and patients with normal percentages of CD21(-) B cells (< 20%; group Ib) revealed a significant clustering of patients with splenomegaly and autoimmune cytopenias in group Ia. Based on these observations, we propose a fast and reliable new classification for CVID patients by flow cytometric quantification of class-switched memory and immature B cells in the peripheral blood of patients. Our results point toward defects at various stages of B-cell differentiation in CVID subgroups and support the value of a B-cell-oriented classification principle. A consensus on this new classification system will hopefully provide a tool for rapidly defining homogeneous subgroups of CVID for functional studies and genetic linkage analysis.

Adult↗

PubMed1996

Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia.

Review of the medical records of 43 patients with common variable immunodeficiency (CVID) and 23 patients with X-linked agammaglobulinemia (XLAG) revealed a high incidence of chronic gastrointestinal complaints, most commonly diarrhea. Thirty-eight biopsies, four small-bowel resection specimens, and one autopsy from 10 patients with CVID and one patient with XLAG showed a wide range of abnormalities. A pattern resembling acute graft-versus-host disease, with apoptotic bodies and lymphocytes in crypts, was seen in the stomach (four patients), small bowel (three patients), and colon (three patients). Small-bowel specimens from three CVID patients with malabsorption showed mild to severe villous atrophy. Three CVID patients had Giardia in biopsies. Two cases of small bowel lymphoma associated with nodular lymphoid hyperplasia were identified in CVID patients. One patient's small bowel contained foamy histiocytes in the lamina propria, resembling Whipple's disease or chronic granulomatous disease, with numerous apoptotic bodies in crypts. Ultrastructurally, the histiocytes contained cellular debris. The patient with XLAG had recurrent fissuring necrosis of small bowel resembling Crohn's disease; a patient with CVID had colitis with features similar to ulcerative colitis. Poorly formed granulomas were seen in the stomach (one CVID patient) and the colon (two CVID patients). Lymphocyte populations were dominated by T cells; B cells were scarce except in lymphoid follicles in CVID patients with nodular lymphoid hyperplasia. Patients with CVID and XLAG manifest a spectrum of abnormalities in the gastrointestinal tract, with patterns superficially resembling graft-versus-host disease, inflammatory bowel disease, and Whipple's disease, but often lacking some of the diagnostic features of the diseases. Many of the CVID patients with chronic gastrointestinal complaints (62%) also had evidence of autoimmune phenomena, suggesting that in some patients the inflammatory process in the gastrointestinal tract has an autoimmune component.

Adolescent↗

PubMed1995

Family and linkage study of selective IgA deficiency and common variable immunodeficiency.

Screening of close relatives of Swedish patients with selective immunoglobulin A deficiency (IgAD) and common variable immunodeficiency (CVID) for serum immunoglobulin levels has identified the positive family history of IgAD/CVID as the most significant risk factor for developing the disease. The relative risk for siblings of patients with IgAD was estimated to be approximately 50. In 12 of 34 Swedish multiplex families identified in the study, both IgAD and CVID occurred, usually CVID in the parental generation and IgAD in the subsequent generation. This proportion was much higher than expected by chance and strongly suggests that the two clinically discernible disorders represent an allelic condition, reflecting a variable expressivity of a common defect. In 27 multiplex families the disorders segregated as an autosomal dominant trait, affecting at least two generations. A high relative risk for siblings, permanent phenotype, low number of phenocopies, and common population prevalence, which makes it possible to obtain a sufficient sample size, make these immunoglobin deficiencies amenable to genetic linkage analysis. In a pilot multicenter linkage study involving 16 multiplex families with dominant transmission of IgAD/CVID, we have attempted to confirm previously reported genetic linkage of the disease susceptibility to the major histocompatibility complex (MHC) region. Using both parametric and nonparametric linkage analyses with a set of microsatellite markers at and flanking the MHC region, no evidence for linkage was found. In accordance with these results, no evidence for linkage to the MHC region was obtained by analyzing previously published segregation data at the MHC region in multiplex families with IgAD/CVID in more than one generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Common Variable Immunodeficiency↗

PubMed1984

Immunological analysis in familial common variable immunodeficiency.

Immunological and genetic studies were performed in nine members from three generations of the family of a patient with common variable immunodeficiency (CVI). Two additional symptomatic members (mother and grandmother) had CVI. Among other six asymptomatic members, two had CVI and one had selective IgA deficiency. The proportions of monoclonal antibody defined total T cells (Leu 1+), helper phenotype (Leu 3+) suppressor phenotype (Leu 2+) T cells, natural killer cells (Leu 7+) and surface Ig+ B cells and proliferative response to phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and in mixed lymphocyte reaction (MLR) were comparable to controls. Addition of purified interleukin-2 (IL-2) resulted in augmentation of PHA-induced proliferation of T lymphocytes similar to that seen in the controls, however with IL-2 freshly isolated T cells in the absence of PHA demonstrated markedly increased proliferative response, suggesting the presence of in vivo activated T cells. Study of HLA phenotype did not reveal any linkage. This study demonstrates the genetic nature, possibly autosomal dominant inheritance, of common variable immunodeficiency; however the immunodeficiency is not linked to any specific HLA antigen.

Adolescent↗

PubMedDate not supplied

Gastric adenocarcinoma in a patient with common variable immunodeficiency.

We describe a 46-year-old man with a 20-year history of common variable immunodeficiency (CVID) who developed adenocarcinoma of the stomach. Although the mechanism is still debated, there is an increased frequency of gastric adenocarcinoma of the stomach in patients with CVID. Consequently, gastric complaints in patients with CVID should be pursued aggressively.

Adenocarcinoma↗

PubMed2006

CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation.

The recently proposed Piqueras classification of common variable immunodeficiency (CVID) patients is based on flow cytometric quantification of IgD class-switched and CD27 membrane-expressing mature blood B cells. But, many patients also have circulating T cells with immunophenotypic abnormalities, often associated with clinical complications, such as splenomegaly, autoimmune disease, lymphoid proliferation and/or granulomatosis. In 50 unselected CIVD patients, classified according to CD27 and IgD B-cell expression, we analyzed T-lymphocyte subsets according to their expression of HLA-DR and intracellular perforin and/or granzyme B in CD8+ T lymphocytes, CCR7 and CD45RA. CD3+DR+ T-lymphocyte percentages, predominantly CD8+DR+, were significantly higher in patients with clinical complications. MB0 classified patients, characterized by fewer CD27+ B cells, had higher percentages of CD8+DR+ T lymphocytes expressing perforin and/or granzyme with a differentiated effector (CCR7- and CD45RA+) phenotype. In contrast, MB2 patients (with normal CD27+ and IgD- B cells) were free of clinical complications and showed no signs of T-cell activation. MB1 patients (normal CD27+ numbers but fewer IgD- B cells) were either clinically normal or had complications. Combining the set of markers described herein might better define homogeneous groups of patients for etiological studies and clearly segregate patients with clinical complications.

Adolescent↗

PubMed2001

Common variable immunodeficiency treated with a recombinant human IgG, tumour necrosis factor-alpha receptor fusion protein.

Common variable immunodeficiency (CVI) is characterized by a failure in B-cell differentiation and impaired immunoglobulin secretion, but with a variable clinical presentation, including the development of sarcoidal granulomas and autoimmune diseases, as well as an increased incidence of malignancies. We present a 21-year-old white man who carried a diagnosis of juvenile rheumatoid arthritis and presented 6 years later with scarring alopecia showing sarcoidal granulomas. Further work confirmed the diagnosis of CVI, and with increasing systemic symptoms, it was elected to treat the patient with a tumour necrosis factor (TNF)-alpha antagonist, a TNF-alpha receptor IgG1 fusion protein. The patient showed improvement in his systemic symptoms and some hair regrowth after 3 months of therapy, and continued improvement in his systemic disease with only mild scalp hair thinning in the areas of prior involvement after almost 1 year of therapy. CVI and sarcoid may have overlapping clinical and immunological findings. Previous therapies for CVI, including intravenous immunoglobulin, have not altered the mortality of the disease. TNF-alpha is a primary cytokine and is elevated in CVI, and specific inhibition of TNF-alpha in this patient was effective in moderating his disease, including his skin disease.

Adult↗

PubMed1996

CD4+ cells from patients with Common Variable Immunodeficiency have a reduced ability of CD40 ligand membrane expression after in vitro stimulation.

BACKGROUND: Common Variable Immunodeficiency (CVID) is characterized by defective antibody production. This has been variably attributed to intrinsic B-cell defects or to T-cell disfunctions. Recently, it has been reported that the expression of the CD40 Ligand (CD40L), a T-cell surface molecule that plays a critical role in the cell-contact-mediated helper signals provided to B-cells, is defective in a subset of patients with CVID. METHODS: To demonstrate that the defective expression is due to intrinsic functional abnormalities of CD4+ lymphocytes, CD4+ cells were purified from eight patients with CVID and eight age-paired controls, stimulated with PMA+Ionomycin, and studied for CD40L expression by flow cytometry using specific monoclonal antibodies. RESULTS AND CONCLUSIONS: The percentage of CD4+ cells expressing CD40L after optimal stimulation was correlated with age both in patients with CVID (r: 0.74; p: 0.04) and in healthy controls (r: 0.73; p: 0.04). The percentage of CD40L+ cells was reduced in patients with CVID compared to that of controls (p: 0.02 when data are paired for age) with a reduced density of expression (p: < 0.01). The defect was variable in different patients and in some cases it was marginal.

Adolescent↗

PubMed1998

[Common variable immunodeficiency associated with autoimmune thrombocytopenia: anesthetic management].

A 44-year-old man diagnosed of common variable immunodeficiency associated with thrombopenia due to autoimmunity required anesthesia for anal fissure repair and hemorrhoidectomy. Hemostatic complications developed after surgery, with extreme thrombopenia (1,000 platelets/pl) and analytical changes that necessitated administration of six units of platelets from apheresis, as well as immunoglobulins, antifibrinolytic agents (e-aminocaproic acid) and granulocytic colony stimulating factors. Anesthesia for such patients is reviewed, with emphasis on careful management of the airways, preparation of sufficient material for surgery (rapid transfusion equipment, large caliber intravenous catheters, sterile material) and orientation of anesthetic technique toward general anesthesia through a laryngeal mask.

Adjuvants, Anesthesia↗

PubMed1996

[Unexplained remission of common variable immunodeficiency: analysis of a clinical case].

We report a 26 years old female with a common variable immunodeficiency diagnosed at the age of 21, with recurrent pulmonary and sinusal bacterial infections, that had a clinical and laboratory remission. At the moment of diagnosis, she had agammaglobulinemia in the protein electrophoresis, very low level of IgG and IgM and absence of IgA. Absolute counts of CD4(+) T lymphocytes were low and CD8(+) were normal. B lymphocyte count was normal. Five years later, a repeated study revealed normal levels of all these parameters, excepting IgA that continued to be undetectable. We propose that the remission could be due to a decrease in suppressor activity of T lymphocytes. There is no documented evidence of infectious factors or the use of immunological therapy that could have influenced the course of the disease.

Adult↗

PubMed2005

Chlamydia pneumoniae arthritis in a patient with common variable immunodeficiency.

BACKGROUND: Arthritis is an important and sometimes life-threatening complication in patients with common variable immunodeficiency (CVID). OBJECTIVE: To describe a patient with CVID and arthritis due to Chlamydia pneumoniae, which is usually regarded as a respiratory tract pathogen and has not previously been detected in the synovial fluid by cell culture technique. METHODS: Routine bacteriologic, virologic, mycologic, and tuberculosis cultures were performed. The patient's synovial fluid was examined for fastidious organisms that might be causative pathogens of arthritis, such as chlamydiae, and special cell culture methods were used. Serologic tests were performed to determine viral and bacteriologic etiology. RESULTS: The patient had a history of recurrent respiratory tract infections, and the latest exacerbation was followed by arthritis. Cytologic examination of the fluid yielded abundant lymphocytes. Chlamydia pneumoniae was detected in synovial fluid specimens by cell culture technique. Her nasopharyngeal swab and sputum culture specimens were also positive for this pathogen. She was diagnosed as having arthritis caused by C pneumoniae and was given antibiotherapy. CONCLUSION: Chlamydia pneumoniae should be kept in mind as a causative pathogen in patients with CVID and arthritis, especially when effusion fluid is full of lymphocytes rather than polymorphonuclear cells and no organism is grown on routine cultures.

Adult↗

PubMed2000

Up-regulation of IL-12 in monocytes: a fundamental defect in common variable immunodeficiency.

We show that LPS-stimulated circulating CD14-positive monocytes from patients with common variable immunodeficiency (CVID) express a higher proportion of intracellular IL-12-positive cells than monocytes from patients with X-linked agammaglobulinemia or normal subjects. We used four-color flow cytometry and measured IL-12 with an Ab to the p40 subunit following stimulation with LPS. The raised IL-12 is associated with an increased frequency of IFN-gamma-positive T cells, but not of IFN-gamma-positive CD56+ NK cells. These increases in frequency of cytokine-positive cells are due to a decrease in the absolute numbers of circulating monocytes and T cells that are negative for IL-12 and IFN-gamma, respectively. The increased frequency of IL-12-positive monocytes appears to be selective because TNF-alpha was not increased, and is thus unlikely to reflect a general activation. Chronic infection is also unlikely to explain our data since cells from X-linked agammaglobulinemia patients with a similar Ig deficiency do not show these changes. Our data suggest a fundamental abnormality in the IL-12/IFN-gamma circuit in CVID, with up-regulation of IL-12 being the "primary" factor. This imbalance is likely to skew the immune response away from Ab production and also explains the failure of CVID T cells to make Ag-specific memory cells and the chronic inflammatory and granulomatous complications that are a feature of CVID. This disease appears to be a rare example of a polarized Th1-type response and may in part be due to a genetic defect in the control of IL-12 production.

Agammaglobulinemia↗

PubMed1988

Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency.

Human-human B cell hybridomas constructed from B lymphocytes of common variable immunodeficiency (CVI) patients and the nonsecreting cell line WIL2/729 HF consistently secrete low levels of Ig and appear to retain a defect characteristic of the CVI patient's B cells. We assessed the differentiative capacity of retinoic acid (RA) on these hybridomas, as well as on hybridomas constructed from normal B cells and from patients with selective IgA deficiency. RA at concentrations varying between 10(-5) and 10(-9) M augmented IgM secretion 4-20-fold from four of four CVI hybridomas tested, but did not affect Ig secretion from normal or IgA-deficiency hybridomas. In support of this elevated Ig secretion, RA enhanced the de novo synthesis of biosynthetically labeled light (kappa) and heavy (mu) Ig (up to 4- and 15-fold, respectively) in the CVI hybridoma line JK32.1. The increase in IgM synthesis/secretion could not be accounted for by RA-induced alteration in the cell cycle. In inducing this increase in IgM production, RA was found to affect two aspects of Ig gene expression: (a) the steady-state levels of heavy and light chain mRNAs were enhanced, and (b) the processing of mu heavy chain transcripts to the secreted mRNA form became favored over the membrane mRNA form. We also show that expression of Leu-17 (CD38), a surface marker that is re-expressed in the late pre-plasma stage of B cell development, was increased by RA from less than 20% to greater than 90% of the total cell population, with a concomitant 4-10-fold augmentation in the mean fluorescence intensity. Changes in both Leu-17 expression and de novo Ig synthesis were prominent by 24 h, but could be observed as early as 8 h after induction. Taken together, our study demonstrates that RA affects a marked alteration in the differentiated state of the CVI hybridoma clones. This finding suggests that retinoids can enhance the functional capabilities of B cells with defects in maturation and support further studies to evaluate their clinical potential in CVI.

B-Lymphocytes↗

PubMed1991

Common variable immunodeficiency is associated with polymorphic markers in the human major histocompatibility complex.

Common variable immunodeficiency (CVI) is a heterogeneous condition characterized by arrest in B cell differentiation. A high frequency of null alleles of the C4 gene has been reported in patients with this disorder. We investigated the restriction fragment length polymorphisms (RFLP) of the MHC class II genes HLA-DRB, DQA, and DQB, the class III gene C4 and the tumour necrosis factor-alpha) (TNF-alpha) gene in 40 Caucasian patients. The results showed an increase in HLA-DR3 in patients (40% vs 30.5%), but, more significantly, there was a striking increase in the number of CVI patients who carried a deletion of the C4A gene (46% vs 25%). In both patients and controls there was strong allelic association between HLA-DR3 and C4A deletion, and HLA-DR3 and TNF-alpha. Our results suggest that genes present on an extended haplotype containing these three polymorphisms contribute to genetic susceptibility to CVI.

Adolescent↗

PubMed1991

Alopecia totalis and vitiligo in common variable immunodeficiency.

Three cases of severe and irreversible alopecia occurring in patients with common variable immunodeficiency are described. In all three cases, hair loss developed after the diagnosis of immune deficiency; one of the patients also had extensive vitiligo. A fourth patient had vitiligo in the absence of alopecia. No change in the alopecia or vitiligo was noted in any patient as a result of immunoglobulin replacement therapy.

Adult↗

PubMed1984

Dissociation in the production of B cell-stimulating factors (BCGF and BCDF) and interleukin 2 by T cells from a common variable immunodeficient patient.

In the course of an analysis of lymphocyte functions of common variable immunodeficiency patients, we found one patient whose T lymphocytes released B cell differentiation factor (BCDF) and B cell growth factor (BCGF) without IL 2 production upon stimulation with Con A. The patient was a 68-yr-old woman with hypo-gamma-globulinemia (IgM: 31 mg/dl, IgG: 223 mg/dl, IgA: 23 mg/dl); she suffered from cryptococcal meningitis and pulmonary tuberculosis with a negative result of skin tests to PPD and cryptococcal antigen. The number of T cells and the ratio of T cell subsets (Leu-2a and Leu-3a) was normal. T cells showed no proliferative response to Con A and a low response to PHA (one-tenth of normal response). The addition of patient T cells to normal T cells did not inhibit the proliferation of normal T cells when stimulated by Con A. The culture supernatant of Con A-stimulated T cells contained no IL 2 activity when assayed by an IL 2-dependent T cell line. Expression of Tac antigen was not impaired by Con A stimulation and the addition of partially purified IL 2 from the supernatant of Jurkat T cell line-induced proliferation of Con A-stimulated T cells, indicating that the defect observed was not in IL 2-responding cells but in IL 2-producing cells. In contrast, the culture supernatant of the T cells stimulated by Con A or PHA contained BCDF activity as much as that of normal T cells when assayed by Cowan I-stimulated normal B cells or the B lymphoblastoid cell line SKW6-CL4. The supernatant also contained BCGF activity. These results suggest that B cell-stimulating factor (BCGF, BCDF) and IL 2 may be synthesized by different subsets of T cells or that the synthesis of those lymphokines are independently regulated in the same cells.

Adult↗

PubMed1978

Adenocarcinoma of the stomach with common variable immunodeficiency syndrome.

Two patients had adenocarcinoma of the stomach in association with common variable immunodeficiency syndrome. There has been an increased prevalence of malignancy in this late-onset immunodeficient state. Similar to five previously reported cases, our patients had gastric carcinoma as a late complication. Further documentation of this association stresses the need for long-term follow-up in this premalignant condition.

Adenocarcinoma↗

PubMed1999

[A case of common variable immunodeficiency that responded to long-term erythromycin chemotherapy].

A 32-year-old woman with common variable immunodeficiency (CVID) accompanied by sinopulmonary infection was evaluated for purulent sputum, cough, and nasal obstruction that did not respond to regular intravenous immunoglobin (IVIG) infusion. Chest X-ray films revealed bronchiectasis affecting both lung bases, and a bacteriological examination of sputum was positive for Pseudomonas aeruginosa. Long-term chemotherapy with erythromycin (EM) was started, and the patient's respiratory symptoms gradually subsided. Sinopulmonary infection is the dominant clinical complication in patients with CVID. This case suggested that long-term EM chemotherapy is useful for the treatment of IVIG-refractory sinopulmonary infection associated with CVID.

Adult↗