scholarly journals Common variable immunodeficiency patients display elevated plasma levels of granulocyte activation markers elastase and myeloperoxidase

2019 ◽  
Vol 33 ◽  
pp. 205873841984338 ◽  
Author(s):  
Jiří Litzman ◽  
Zita Chovancová ◽  
Petr Bejdák ◽  
Marek Litzman ◽  
Zdeněk Hel ◽  
...  
Keyword(s):  
Common Variable Immunodeficiency ◽  
Plasma Levels ◽  
Cell Activation ◽  
Acute Infection ◽  
Stable State ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Activation Markers ◽  
Common Variable ◽  
Ivig Administration

Common variable immunodeficiency disorders (CVIDs) represent a group of primary immunodeficiency diseases characterized by hypogammaglobulinemia and dysfunctional immune response to invading pathogens. Previous studies have indicated that CVID is associated with microbial translocation and systemic myeloid cell activation. The goal of this study was to determine whether patients with CVID display elevated systemic levels of markers of granulocyte activation and whether the levels are further influenced by intravenous immunoglobulin (IVIg) infusions. The plasma levels of granulocyte activation markers elastase and myeloperoxidase were determined using enzyme-linked immunosorbent assay (ELISA) in 46 CVID patients and 44 healthy controls. All CVID patients were in a stable state with no apparent acute infection. In addition, granulocyte activation markers’ plasma levels in 24 CVID patients were determined prior to and 1 h following IVIg administration. Neutrophil elastase and myeloperoxidase plasma levels were significantly higher in CVID patients than in healthy controls. Systemic elastase levels were further increased following IVIg administration. In vitro stimulation of 13 CVID patients’ whole blood using IVIg in a therapeutically relevant dose for 2 h resulted in a significant increase in plasma elastase levels compared to unstimulated blood. The data presented here indicate that CVID is associated with chronic granulocytic activation which is further exacerbated by administering IVIg. Increased myeloperoxidase and elastase levels may contribute to associated comorbidities in CVID patients.

scholarly journals Oxidative stress in common variable immunodeficiency

2021 ◽  
Vol 19 ◽  
pp. 205873922110024
Author(s):  
Sevgen Tanir Basaranoglu ◽  
Sukru Cekic ◽  
Emine Kirhan ◽  
Melahat Dirican ◽  
Sara S. Kilic
Keyword(s):  
Oxidative Stress ◽  
Common Variable Immunodeficiency ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Infectious Complications ◽  
Clinical Syndrome ◽  
University Hospital ◽  
Unknown Etiology ◽  
Healthy Controls ◽  
Oxidative Stress Biomarkers ◽  
Common Variable

Common variable immunodeficiency (CVID) is a heterogenous group of immunologic disorders of unknown etiology. Alterations of the normal cellular balance due to an increase in reactive oxygen species and/or decrease in antioxidant defense may lead to increased oxidative stress. We aimed to evaluate the levels of oxidative stress biomarkers in patients with CVID who had different presentations. We investigated the serum catalase (CAT), erythrocyte superoxide dismutase (SOD), erythrocyte reduced glutathione as antioxidants and serum malondialdehyde levels as lipid peroxidation marker in patients with CVID in Uludag University Hospital Department of Pediatric Allergy and Immunology’s outpatient clinics. In the analysis, there were 21 patients and 27 matched healthy controls. The median levels of CAT in patients with CVID was significantly lower than in healthy controls ( p = 0.04). Among the patients with CVID, 19% had autoimmune disease, one had Sjögren’s syndrome, one had autoimmune alopecia, one had juvenile rheumatoid arthritis, and one had chronic inflammatory demyelinating polyneuropathy. Patients with autoimmune complications had significantly lower CAT levels compared to the ones without autoimmune diseases ( p = 0.03). The patients without non-infectious complications (NICs) had lower SOD levels than the patients with NICs ( p = 0.05). The analysis of oxidative stress markers in the patients with CVID suggested a series of abnormalities in the anti-oxidant system. The clinical syndrome associations may be a useful tool for future studies to set prediction markers for the prognosis of patients with CVID.

scholarly journals Increased Expression of B Lymphocyte Induced Maturation Protein 1 (BLIMP1) in Patients with Common Variable Immunodeficiency (CVID)

2020 ◽  
Author(s):  
Shockrollah Farrokhi ◽  
Faezeh Abbasi-rad ◽  
Nafiseh Esmaeil ◽  
Roya Sherkat ◽  
Reza Yazdani ◽  
...  
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Healthy Controls ◽  
Maturation Protein ◽  
Mrna And Protein Expression ◽  
Common Variable

Common variable immunodeficiency (CVID) is a primary immune deficiency disorder characterized by a failure in B cell differentiation, impaired immunoglobulin production, and defect in response to vaccines. As a result of defective B cell maturation and differentiation in CVID, the affected patients commonly present with reduced numbers of memory B cell and antibody-secreting plasma cells. B-cell lymphoma 6 protein (BCL6) and B lymphocyte induced maturation protein 1 (BLIMP1) molecules are two important transcription factors that have key roles in the maturation of B cells to plasma cells. Hence, in the current survey, we aimed to evaluate the mRNA and protein expression levels of BCL6 and BLIMP1 in B lymphocytes isolated from peripheral blood in CVID patients. We collected blood samples from 12 CVID patients and 12 healthy controls. We isolated peripheral blood mononuclear cells (PBMCs) using Ficoll density gradient separation. Then, CD19+ B cells were purified using MACS. The protein expression and transcriptional level of BCL6 and BLIMP1 were respectively measured using flow cytometry and real-time PCR. Our results showed that the BLIMP1 mRNA expression, as well as BLIMP1 protein expression, were significantly higher in CVID patients compared to control subjects (p=0.009 and p=0.007, respectively). However, we found no significant difference in mRNA and protein expression of BCL6 between patients and healthy controls. According to our findings, increased mRNA and protein expression levels of BLIMP1 could be involved in defective maturation of B cells in patients with CVID and elucidate mechanistic insights into the pathogenesis of this disorder.

scholarly journals The Food Additive tBHQ Impairs NK Cell Cytotoxicity Against Influenza Infection (FS12-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Allison Boss ◽  
Robert Freeborn ◽  
Sheng Liu ◽  
Joseph Zagorski ◽  
Alexandra Turley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nk Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Influenza Infection ◽  
Control Diet ◽  
Granzyme B ◽  
Influenza Virus Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Activation Markers

Abstract Objectives We examined the effects of the food preservative, tert-Butylhydroquinone (tBHQ), on natural killer (NK) cells when infected with influenza in C57Bl/6 mice. Previously, we found tBHQ to negatively impact splenic NK cell effector function in vitro. Therefore, we hypothesized that the consumption of tBHQ would impair the NK cell response against a primary influenza virus infection. Methods Female, C57Bl/6 mice were fed either a diet containing 0.0014% tBHQ or a control diet two weeks prior to infection. Mice were instilled intranasally with 21.78 HAU of influenza A/PR/8/34 (H1N1) and were monitored for two days. Body weight was recorded as a measurement for infection. After day two of infection, lungs were collected and processed for analysis by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and total antioxidant capacity (TAC). Results The NK cell activation markers, CD25 and CD69, were not affected by tBHQ consumption. Additionally, tBHQ did not have an effect on maturation of NK cells or interferon (IFN)γ production. Notably, NK cell expression of granzyme B was significantly decreased with tBHQ in infected mice. Furthermore, mice on the tBHQ diet showed decreased TAC after two days of infection compared to mice on the control diet, suggesting increased oxidative stress in the tBHQ group. Conclusions tBHQ had no effect on NK cell activation, maturation, and IFNγ production after two days of influenza infection. However, decreased expression of granzyme B by NK cells suggests tBHQ may impair NK cell cytoxicity during the infection. Moreover, the decrease in TAC suggests increased oxidative stress in the tBHQ-treated mice. Funding Sources This study was funded by National Institute of Environmental Health Sciences (ES024966).

T-cell activation defect in common variable immunodeficiency: Restoration by phorbol myristate acetate (PMA) or allogeneic macrophages

1987 ◽  
Vol 44 (2) ◽  
pp. 206-218 ◽  
Author(s):  
Walter Fiedler ◽  
Karl W. Sykora ◽  
Karl Welte ◽  
Jonathan E. Kolitz ◽  
Charlotte Cunningham-Rundles ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Phorbol Myristate Acetate ◽  
Common Variable Immunodeficiency ◽  
Cell Activation ◽  
Myristate Acetate ◽  
Common Variable

scholarly journals Salivary Immunoglobulins in Individuals with Common Variable Immunodeficiency

2016 ◽  
Vol 27 (6) ◽  
pp. 641-645 ◽  
Author(s):  
Karin Sá Fernandes ◽  
Michella Bezerra Lima ◽  
Cíntia de Paula Martins ◽  
Maria Cristina dos-Santos ◽  
Fabio Daumas Nunes ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Common Variable Immunodeficiency ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Salivary Iga ◽  
Serum Iga ◽  
Whole Saliva ◽  
Few Data ◽  
Immunoglobulin Levels ◽  
Common Variable

Abstract Oral manifestations of common variable immunodeficiency (CVID) are rare, have rarely been studied and have given controversial results. There are few data about IgA, IgG, and IgM antibody salivary levels in the literature, and there are few papers about the clinical impact of antibody deficiencies and CVID on the oral health of such patients. The aim of this study was to measure serum and salivary IgA, IgG, and IgM levels in CVID participants and controls, and to associate immunoglobulin levels with caries and periodontal disease. This was a case-control study involving 51 CVID individuals and 50 healthy controls. All participants underwent examination for dental caries and periodontal disease. Blood and whole saliva samples were collected on the same day of the oral examination. Serum IgA, IgM, and IgG levels were measured by turbidimetry and salivary IgA, IgM, and IgG titers were assessed by enzyme-linked immunosorbent assay. Incidences of caries and gingivitis were significantly higher in the CVID group than in the control group (p<0.05). Salivary and blood IgA and IgM titers were significantly reduced in the CVID group, but there was no association of salivary immunoglobulin levels with periodontal disease or with caries incidence (p>0.05 for both). Although CVID was associated with increased susceptibility to caries and gingivitis, it was not associated with low salivary levels of IgA and IgM.

scholarly journals Chronically Activated T-cells Retain Their Inflammatory Properties in Common Variable Immunodeficiency

2021 ◽  
Author(s):  
Roos-Marijn Berbers ◽  
M. Marlot van der Wal ◽  
Joris M. van Montfrans ◽  
Pauline M. Ellerbroek ◽  
Virgil A. S. H. Dalm ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Common Variable Immunodeficiency ◽  
Immune Activation ◽  
Cell Activation ◽  
Immune Dysregulation ◽  
Negative Regulators ◽  
Migratory Capacity ◽  
Common Variable

Abstract Purpose Immune dysregulation complications cause significant morbidity and mortality in common variable immunodeficiency (CVID), but the underlying pathophysiology is poorly understood. While CVID is primarily considered a B-cell defect, resulting in the characteristic hypogammaglobulinemia, T-cells may also contribute to immune dysregulation complications. Here, we aim to further characterize T-cell activation and regulation in CVID with immune dysregulation (CVIDid). Methods Flow cytometry was performed to investigate T-cell differentiation, activation and intracellular cytokine production, negative regulators of immune activation, regulatory T-cells (Treg), and homing markers in 12 healthy controls, 12 CVID patients with infections only (CVIDio), and 20 CVIDid patients. Results Both CD4 + and CD8 + T-cells in CVIDid showed an increased activation profile (HLA-DR + , Ki67 + , IFNγ +) when compared to CVIDio, with concomitant upregulation of negative regulators of immune activation PD1, LAG3, CTLA4, and TIGIT. PD1 + and LAG3 + subpopulations contained equal or increased frequencies of cells with the capacity to produce IFNγ, Ki67, and/or GzmB. The expression of PD1 correlated with serum levels of CXCL9, 10, and 11. Treg frequencies were normal to high in CVIDid, but CVIDid Tregs had reduced CTLA-4 expression, especially on CD27 + effector Tregs. Increased migratory capacity to inflamed and mucosal tissue was also observed in CVIDid T-cells. Conclusion CVIDid was characterized by chronic activation of peripheral T-cells with preserved inflammatory potential rather than functional exhaustion, and increased tissue migratory capacity. While Treg numbers were normal in CVIDid Tregs, low levels of CTLA-4 indicate possible Treg dysfunction. Combined studies of T-cell dysfunction and circulating inflammatory proteins may direct future treatment strategies.

scholarly journals Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency--possible immunologic and clinical consequences

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 674-681 ◽  
Author(s):  
P Aukrust ◽  
E Lien ◽  
AK Kristoffersen ◽  
F Muller ◽  
CJ Haug ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Common Variable Immunodeficiency ◽  
Peripheral Blood ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Tnf Alpha ◽  
Healthy Controls ◽  
Necrosis Factor ◽  
Common Variable

In patients with common variable immunodeficiency (CVI), we have previously defined a subgroup of patients (CVIHyper) characterized by decreased numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune activation in vivo, particularly of monocytes/macrophages. To further characterize this hyperactivity, parameters of activation of the tumor necrosis factor (TNF) system (TNF alpha and soluble TNF receptors [sTNFRs]) were measured in 24 patients with CVI and 20 healthy controls. Patients with CVI had significantly higher serum levels of TNF alpha and both types of sTNFRs, with the highest levels in the CVIHyper subgroup. In vitro, peripheral blood mononuclear cells (PBMC) and purified monocytes from CVIHyper patients spontaneously released significantly higher levels, and, after lipopolysaccharide (LPS) stimulation, significantly lower levels of TNF alpha and soluble p75-TNFR than cells from both other CVI patients and healthy controls. CVIHyper patients also had significantly higher TNF alpha:sTNFRs ratios in both serum and in unstimulated PMBC supernatants. The present study demonstrates persistent in vivo activation of the TNF system in CVI, particularly in the CVIHyper subgroup. This activation may contribute to the pathogenesis of both clinical and immunologic manifestations in CVI.

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