Immune thrombocytopenia: serum cytokine levels in children and adults (original) (raw)
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Altered cytokine levels in pediatric ITP
Platelets, 2015
Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children, the disease resolves, but in some, it becomes chronic. Cytokines are important mediators of the immune response and are known to be dysregulated in autoimmune diseases. Therefore, our aim was to investigate differences in plasma levels of cytokines between children with ITP and healthy controls. We had two cohorts of children: one Swedish with 18 children with ITP and seven healthy children and a second Chinese one with 58 children with ITP and 30 healthy children. Plasma levels of chemokine (C-X3-C motif) ligand 1 (CX3CL1), transforming growth factor b1 (TGF-b1), and interleukin 22 (IL-22) were analyzed in both cohorts using enzyme-linked immunosorbent assays (ELISAs). We found lower plasma levels of TGF-b1 and elevated levels of CX3CL1 and IL-22 in children with ITP compared with controls in both the Swedish and the Chinese cohort. In conclusion, all three cytokines differ between pediatric ITP and healthy controls and may, therefore, be potential biomarkers for the disease.
Suez Canal University Medical Journal
Background: Immune thrombocytopenia (ITP) is a common acquired autoimmune disease in which autoantibody-coated platelets induce phagocytosis by macrophages. Complex immune dysregulation including Th1/Th2 imbalance is involved in the pathogenesis of this disease. Tumor necrosis factor-alpha (TNF-α) and interleukin 4 (IL-4) are cytokines produced by T cells and have various inflammatory, and immunomodulatory activities. Aim: To detect the changes in the level of TNF-α and IL-4in children with immune thrombocytopenia, and to correlate their levels with the disease course, severity, and response to treatment. Subjects and Methods: This is a case-control study that enrolled 100 subjects divided into 2 groups; patients' group: children with ITP and age-and gender-matched normal subjects as control. All participants were subjected to complete blood count, assessment of serum TNF-α, and IL-4 using ELISA technique. Results: There was a non-significant difference between patients and control groups (p-value 0.283) in serum IL-4; moreover, there was a non-significant difference in IL-4 levels among different severity grades of ITP. On the other hand, serum TNF-α was significantly higher in the patients' group than in the control group (p-value 0.002). Both TNF-α and IL-4 levels were significantly higher in newly diagnosed patients. Conclusion: TNF-α levels increase in patients with ITP. TNF-α and IL-4 are significantly higher in patients with newly diagnosed ITP.
Clinical & Experimental Immunology, 2014
Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3 + , CD4 + , CD8 +) and B (CD19 +) lymphocytes, natural killer (NK) (CD16 + 56 +) and regulatory T (Treg) [CD4 + CD25 +high forkhead box protein 3 (FoxP3) + ] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF-α)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Treg (P < 0•001) and natural killer (NK) (P < 0•001) cells were significantly decreased in ITP patients compared to healthy controls. A negative correlation was reported between the percentage of Treg cells and development of acute (r = −0•737; P < 0•01) and chronic (r = −0•515; P < 0•01) disease. All evaluated cytokines (IFN-γ, TNF-α, IL-4, IL-6 and IL-10) were elevated significantly in ITP patients (P < 0•001, P < 0•05, P < 0•05, P < 0•05 and P < 0•001, respectively) compared to controls. In conclusion, our data shed some light on the fundamental role of immune cells and their related cytokines in ITP patients. The loss of tolerance in ITP may contribute to the dysfunction of Tregs. Understanding the role of T cell subsets will permit a better control of autoimmunity through manipulation of their cytokine network.
Pediatric Blood & Cancer, 2017
Background: Immune thrombocytopenic purpura (ITP) is characterized by a transient (nonchronic) or permanent (chronic) decline in the number of platelets. Predicting the course of ITP, at the time of diagnosis, is of importance. Here we studied at diagnosis, clinical and immunological parameters in order to distinguish between different courses. The latter included the measure of new B and T cells using quantification of kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs), respectively. Methods: Blood samples were collected from 44 children with a clinical diagnosis of ITP. Realtime PCR was performed in order to quantify the number of copies of TREC and KREC followed by collection of clinical data from medical files. The children were retrospectively divided into two groups: chronic and nonchronic. Results: Twenty-four patients (54%) were classified as nonchronic ITP and 20 patients (46%) were classified as chronic ITP. We confirmed some clinical parameters (e.g., gender, age) but not others (e.g., preceding infection, level of thrombocytopenia) that distinguish patients with chronic and nonchronic course. While KREC quantification was similar in patients regardless the outcome of their disease, it was significantly higher than the level of controls (P < 0.05). TREC quantification was not different between patients and controls. Conclusions: KREC but not TREC levels are different in patients comparing to controls, pointing to an overreaction of B-cell development as a role in the pathogenesis of ITP. These results may shed more lights on the immune mechanism of ITP.
Blood Coagulation & Fibrinolysis, 2016
To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6S174 CC [P U 0.0001, odds ratio (OR) U 7.048, 95% confidence interval (CI) U 2.18-22.7], higher GA genotype of TNF-a (S308) (P U 0.001, OR U 6.469, 95% CI U 2.0-20.9), higher CC genotype of IL-17F (P U 0.0001, OR U 55.545, 95% CI U 14.4-213.2), higher GG of IL-10S1082 (P U 0.029, OR U 3.6, 95% CI U 1.08-12.18), and A1A2 genotype of IL-1Ra VNTR (P U 0.039, OR U 2.374, 95% CI U 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P U 0.042, P U 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.
Journal of Pediatric Hematology/Oncology, 2013
Primary immune thrombocytopenia (ITP) is one of the most common bleeding disorders of childhood. In most cases, it presents with sudden widespread bruising and petechiae in an otherwise well child. Thought to be mainly a disorder of antibodymediated platelet destruction, ITP can be self-limited or develop into a chronic condition. In this review, we discuss current concepts of the pathophysiology and treatment approaches to pediatric ITP.
European Journal of Pediatrics, 2023
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the breakdown of immune tolerance. Impairment of the cellular immunity is primarily evaluated by the levels of the cytokines which can help in predicting the course of ITP. We aimed to assess the levels of IL4 and IL6 in children with ITP and evaluate their role in the pathogenesis and prognosis of this disease. A prospective cohort study was carried on 60 children (15 patients with newly diagnosed ITP, 15 patients with persistent ITP, 15 patients with chronic ITP and 15 healthy children as a control group). Serum IL-4 and serum IL-6 were measured using Human IL-4 and IL-6 ELISA kit in patients and controls. Patients with newly diagnosed and persistent ITP had significantly higher levels of IL4 and IL6 compared to patients with chronic ITP and healthy controls (p < 0.001). The mean serum level of IL4 was 762.0, 741.0, 364.6 and 436.8 pg/ml, and the mean serum level of IL6 was 178.5, 164.4, 57.9 and 88.4 pg/ml for patients with newly diagnosed, persistent, chronic ITP and healthy controls respectively. Serum IL-4 was significantly higher in patients who achieved remission than those who did not improve on first line therapy. Conclusion: Serum IL-4 and IL-6 may have a role in the pathogenesis of primary ITP. IL-4 seems to be a good predictor to treatment response. What Is Known: • There is a delicate balance of specific cytokine levels in immune thrombocytopenia, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. changes in IL-4 and IL-6 might be involved in the pathogenesis of newly diagnosed ITP in both paediatric and adult patients. • We conducted this research study to measure the serum level of IL-4 and IL-6, in newly diagnosed, persistent and chronic ITP patients and study their relation to disease pathogenesis as well as patient's outcome. What Is New: • We found that IL4 seems to be a good predictor to treatment response and it was a very interesting observation in our study, and to the best of our knowledge, there is no published data about this finding.
The Egyptian Journal of Hospital Medicine
Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease mediated by antiplatelet autoantibodies that cause platelet destruction and suppression of platelet production. Tumor necrosis factor alpha (TNF-α) is a multifunctional cytokine and is involved in the promotion of inflammatory responses. It also plays critical roles in the pathogenesis of autoimmune diseases. Objective: To assess the level of TNF-α in children with primary ITP and its contribution to pathogenesis of the disease. Patients and Methods: A case control study was conducted on 21 ITP patients (13 males and 8 females) and twenty age-and sex-matched healthy children as a control group at the
Interleukin 27 Serum Level And Its Prognostic Significance In Children With Immune Thrombocytopenia
Zagazig University Medical Journal, 2019
Aim of the work: was to determine the level of IL-27 in patients with immune thrombocytopenia and its relationship to demographic,clinical and laboratory characteristics of patients as well as disease chronicity and response to treatment. Methods: A case control study carried out in Pediatric Hematology outpatient clinic , Zagazig University Hospitals. It included 80 subjects were divided into 4 group 1 included 20 patients with denovo ITP, group 2 included 20 patients with chronic ITP, group 3 included 20 patients with complete remission after 1st line therapy and group 4 (control group) included 20 healthy children as a control group. Results: there is significant difference regarding WBCs and Platelets, there was no significant difference in patients with ITP as regards hemoglobin level. ITP patients had significantly higher levels of IL-27 than controls. Patients with acute ITP had the highest levels of IL-27 among patient groups ,while, patients in remission had the lowest IL-27 levels among patient groups. There was significant relationship between 1st line therapy and serum IL-27 in patients with ITP. Patients who received IVIG and combined steroids and IVIG had significantly higher IL-27 levels than others. There was significant relationship between 2nd line therapy and serum IL-27 in patients with chronic ITP. Where patients who received Eltrombopag had significantly lower IL-27 levels than others. Conclusion: we propose that the using of IL-27 as a predictor for ITP occurrence and for responsiveness to treatment but this need to be confirmed in larger studies.