Modulation of the Interleukin-21 Pathway with Interleukin-4 Distinguishes Common Variable Immunodeficiency Patients with More Non-infectious Clinical Complications

2017 ◽  
Vol 38 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Marylin Desjardins ◽  
Marianne Béland ◽  
Marieme Dembele ◽  
Duncan Lejtenyi ◽  
Jean-Phillipe Drolet ◽  
...  
Keyword(s):  
Common Variable Immunodeficiency ◽  
Interleukin 4 ◽  
Clinical Complications ◽  
Interleukin 21 ◽  
Common Variable

Characterization of Common Variable Immunodeficiency (CVID) Subgroups through Modulation of Their Interleukin-21 (aCD40/IL-4/IL-21) Pathway in Vitro

2015 ◽  
Vol 135 (2) ◽  
pp. AB91
Author(s):  
Marylin Desjardins ◽  
Marianne Beland ◽  
Jean-Philippe Drolet ◽  
Reza Alizadehfar ◽  
Bruce D. Mazer
Keyword(s):  
Common Variable Immunodeficiency ◽  
Interleukin 21 ◽  
Common Variable

scholarly journals Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4760
Author(s):  
Giuliana Amato ◽  
Federica Vita ◽  
Paolina Quattrocchi ◽  
Paola Lucia Minciullo ◽  
Giovanni Pioggia ◽  
...  
Keyword(s):  
Common Variable Immunodeficiency ◽  
Bacterial Infections ◽  
Infectious Complications ◽  
Knock Out ◽  
Scientific Databases ◽  
Clinical Complications ◽  
Mesh Terms ◽  
Bibliographic Search ◽  
Epigenetic Phenomenon ◽  
Common Variable

Background and objectives: Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories. The aim of this study was to review the role of microRNAs (miRNAs) in CVID, focusing on the involvement of the same miRNAs in various non-infectious clinical complications of CVID, mainly autoimmunity and/or cancer. Materials and Methods: A bibliographic search of the scientific literature was carried out independently by two researchers in scientific databases and search engines. The MeSH terms “microRNAs” and “common variable immunodeficiency” were used. All research articles from inception to May 2020 were considered. Results: The literature data showed the involvement of two miRNAs in primary immunodeficiency: miR-142 and miR-155. Both of these miRNAs have been investigated through mice models, in which miR-142 and miR-155 were deleted. These knock-out (KO) mice models showed phenotypic analogies to CVID patients with hypogammaglobulinemia, adaptive immunodeficiency, polyclonal proliferation, lung disease, and enteric inflammation. miR-142 and miR-155 have been found to be involved in the following autoimmune and neoplastic clinical complications of CVID: Gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, natural killer/Tcell lymphoma (NKTCL), and immune thrombocytopenia. Conclusions: miR-142 and miR-155 deregulation leads to similar CVID phenotypesin KO mice models. Although no data are available on the involvement of these miRNAs in human CVID, their dysregulation has been detected in human CVID comorbidities. The literature data show that miRNA sequences in murine models are comparable to those in humans; therefore, miR-142 and miR-155 involvement in human CVID could be hypothesized.

scholarly journals Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jan Stuchlý ◽  
Veronika Kanderová ◽  
Marcela Vlková ◽  
Ivana Heřmanová ◽  
Lucie Slámová ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Common Variable Immunodeficiency ◽  
Cd4 T Cells ◽  
Genetic Background ◽  
Color Flow ◽  
Phenotypic Profile ◽  
Clinical Complications ◽  
T Cell Phenotypes ◽  
Common Variable

Abstract Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning “bins” yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in naïve CD4+ T-cells (decreased), intermediate CD27− CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes’ immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ CD4+ T-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background.

scholarly journals Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?

2017 ◽  
Vol 54 (6) ◽  
pp. 636-643
Author(s):  
Elif Azarsız ◽  
Neslihan Karaca ◽  
Erturk Levent ◽  
Necil Kutukculer ◽  
Eser Sozmen
Keyword(s):  
Common Variable Immunodeficiency ◽  
Intima Media Thickness ◽  
Primary Immunodeficiency Disorder ◽  
Amyloid A ◽  
Clinical Complications ◽  
Performance Indexes ◽  
Significant Difference ◽  
Chitotriosidase Activity ◽  
Common Variable

Background Common variable immunodeficiency is a rare clinically symptomatic primary immunodeficiency disorder which manifests a wide variability of symptoms, complications. Atherosclerosis in common variable immunodeficiency patients has not been investigated yet contrary to other severe clinical complications. We aimed to investigate the chitotriosidase enzyme's role as an inflammation and atherosclerosis marker in paediatric common variable immunodeficiency patients. Methods Common variable immunodeficiency patients (n = 24) and healthy controls (n = 23) evaluated for chitotriosidase activity with other inflammation markers (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and echocardiographic findings (carotid artery intima media thickness – cIMT, brachial artery flow-mediated vazodilatation – FMD%). Results In patients, the mean chitotriosidase activity (8.98 ± 6.28) was significantly higher than the controls (5.17 ± 3.42) ( P = 0.014). Chitotriosidase showed positive relation with hs-CRP ( P = 0.011) and SAA ( P = 0.011) but had no relation with ferritin ( P = 0.155), HDL ( P = 0.152) or LDL-cholesterol ( P = 0.380). Mean cIMT increased in patients compared with the controls ( P < 0.001) but did not show any relation with chitotriosidase ( P = 0.546). FMD% decreased in patients ( P < 0.001) also showing no relation with chitotriosidase ( P = 0.298). Ventricular myocardial performance indexes had no significant difference, but RVEF% decreased in patients ( P = 0.043). Conclusions High chitotriosidase activity in common variable immunodeficiency patients demonstrated in vivo the presence of activated macrophages indicating ongoing inflammation. Echocardiographic diastolic functional deficiency, increased cIMT and decreased FMD% may be accepted as early atherosclerotic findings, but none of them showed relationship with chitotriosidase activities.

scholarly journals Evaluation of miR-210 expression in common variable immunodeficiency: patients with unsolved genetic defect

2021 ◽  
Vol 49 (2) ◽  
pp. 84-93
Author(s):  
Fateme Babaha ◽  
Reza Yazdani ◽  
Sepideh Shahkarami ◽  
Zahra Hamidi Esfahani ◽  
Hassan Abolhahassani ◽  
...  
Keyword(s):  
Common Variable Immunodeficiency ◽  
Genetic Defect ◽  
Foxp3 Expression ◽  
Control Group ◽  
Genetic Defects ◽  
Healthy Individuals ◽  
Primary Immunodeficiency Diseases ◽  
Foxp3 Mrna ◽  
Clinical Complications ◽  
Common Variable

Background: Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency diseases (PID). CVID is characterized by failure in the final differentiation of B lymphocytes and impaired antibody production but the pathogenesis is not known in the majority of patients. We postulated that the expression pattern of miRNAs in unsolved CVID patients might be the underlying epigenetic cause of the disease. Therefore, we aimed to assess the expression of hsa-miR-210-5p and FOXP3 transcription factor in CVID cases in comparison with healthy individuals. Methods: Eleven CVID cases with no genetic defects (all PID known genes excluded) and 10 sex and age-matched healthy individuals were enrolled in the study. T lymphocytes were purified from PBMC, and expression levels of miR-210-5p and FOXP3 mRNA were evaluated by real-time PCR. Results: We demonstrated that miR-210 expression in patients was significantly higher than the control group (P = 0.03). FOXP3 expression was slightly lower in patients compared with healthy controls (P = 0.86). There was a negative correlation between miR and gene expression (r: −0.11, P = 0.73). Among various clinical complications, autoimmunity showed a considerable rate in high-miR patients (P = 0.12, 42.8%), while autoimmunity was not observed in normal miR-210 patients. Conclusions: Our results suggest a role for miR-210 in the pathogenesis of autoimmunity in CVID patients. Further studies would better elucidate epigenetic roles in CVID patients with no genetic defects.

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