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 Differently expressed microRNA in response to the first Ig replacement therapy in common variable immunodeficiency patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bruna De Felice ◽  
Ersilia Nigro ◽  
Rita Polito ◽  
Francesca Wanda Rossi ◽  
Antonio Pecoraro ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Common Variable Immunodeficiency ◽  
Antigen Processing ◽  
Serum Samples ◽  
Primary Immunodeficiency Disorder ◽  
Class I Mhc ◽  
Treatment Naïve ◽  
Delays In Diagnosis ◽  
First Time ◽  
Common Variable

AbstractCommon variable immunodeficiency (CVID) is a complex primary immunodeficiency disorder characterized by a high clinical and genetic heterogeneity. The molecular underlying causes of CVID are not still now clear and the delays in diagnosis and treatment worsen the prognosis of the patients. MicroRNAs are non-coding, endogenous small RNAs often deregulated in human diseases, such as autoimmune and other immune-based disorders. In the present study, we aimed to evaluate miRNAs associated with the CVID and, in particular, with the response to the first Ig replacement therapy. To this aim, we compared miRNA profile obtained by serum samples of treatment-naïve CVID patients before and 24 h after the first Ig replacement therapy. For the first time, using a microarray assay followed by an integrated bioinformatics/biostatistics analysis, we identified five microRNAs (hsa-miR-6742, hsa-miR-1825, hsa-miR-4769-3p, hsa-miR-1228-3p, hsa-miR-1972) differently modulated in CVID patients by Ig infusion. All of them were down-regulated, excepted miR-6742 which was up-regulated. The latter may be of particular interest, since its functions are related to pathways involving Class I MHC mediated antigen processing and adaptive as well as innate Immune System. In conclusion, this study shows for the first time the modulation of miRNAs involved in CVID patients after the first Ig replacement therapy. Further studies are needed to assess whether such miRNAs could represent novel potential biomarkers in management and therapy of CVID patients.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

2020 ◽  
Vol 181 (9) ◽  
pp. 706-714 ◽  
Author(s):  
Mohammad Hossein Asgardoon ◽  
Gholamreza Azizi ◽  
Reza Yazdani ◽  
Mahsa Sohani ◽  
Salar Pashangzadeh ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Common Variable Immunodeficiency ◽  
Primary Immunodeficiency Disorder ◽  
Immunodeficiency Disorder ◽  
Common Variable

13-Cis retinoic acid enhances in vivo B-lymphocyte differentiation in patients with common variable immunodeficiency

1991 ◽  
Vol 88 (5) ◽  
pp. 705-712 ◽  
Author(s):  
Daniel C. Adelman ◽  
Tommy Y. Yen ◽  
William G. Cumberland ◽  
Neil Sidell ◽  
Andrew Saxon
Keyword(s):  
Retinoic Acid ◽  
Common Variable Immunodeficiency ◽  
B Lymphocyte ◽  
Lymphocyte Differentiation ◽  
Common Variable

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

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 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.

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 Characterization of common variable immunodeficiency: identification of a subset of patients with distinctive immunophenotypic and clinical features [see comments]

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2046-2051 ◽  
Author(s):  
JJ Wright ◽  
DK Wagner ◽  
RM Blaese ◽  
C Hagengruber ◽  
TA Waldmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Features ◽  
Cd8 T Cells ◽  
Common Variable Immunodeficiency ◽  
Interleukin 2 ◽  
Delayed Type Hypersensitivity ◽  
Activation Markers ◽  
Common Variable

The peripheral blood lymphocyte surface markers and clinical features of 38 patients with common variable immunodeficiency (CVID) were assessed. These studies identified a subset of CVID consisting of 14 of the 38 patients with a distinctive T-cell immunophenotype and clinical findings. The phenotypic changes were characterized by an abnormally low CD4/CD8 ratio (less than or equal to 0.9) due primarily to a significant increase in CD8 T cells. In addition, there was an expansion in CD8 T cells coexpressing CD57 and increased expression of the activation markers HLA-DR and interleukin-2 receptor (IL-2R) by these cells. This group of immunophenotypically abnormal CVID patients also had characteristic clinical features, including splenomegaly (P less than .02) and in vivo T-cell dysfunction based on the evaluation of delayed-type hypersensitivity (P less than .05). Approximately 71% of these patients had splenomegaly and 42% were anergic in contrast to the remaining group of CVID patients, in which 29% had splenomegaly and 7% were anergic. These findings define a subgroup of CVID patients that have specific immunophenotypic features and functional T-cell abnormalities.

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