Quantification of specific T and B cells immunological markers in children with chronic and transient ITP (original) (raw)
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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.
Assessment of Regulatory T Cells in Childhood Immune Thrombocytopenic Purpura
ISRN Hematology, 2013
This study had the objective to assess the frequency of Tregs in children newly diagnosed with ITP and ascertain whether an association exists between Tregs and platelet counts, by means of a comparison with healthy controls. This case-control study included 19 patients newly diagnosed with ITP-whose blood samples were collected at four points in time: before any therapy and 1, 3, and 6 months after diagnosis-and 19 healthy controls. Tregs (CD4 + CD25 + Foxp3 T cells) were evaluated by flow cytometry. There was a statistically significant difference in platelet count between the case and control groups. There were no significant differences in Treg counts between cases and controls at any point during the course of the study and no difference in Treg counts between the chronic and nonchronic groups and no significant correlation between Tregs and platelet counts in the case and control groups. The findings of this study did not show any statistically significant correlation between Tregs and number of platelets in the case and control groups. Treg cells did not play a role in the regulation of autoimmunity in children with ITP.
Asthma Allergy Immunology
Objective: Primary Immune Thrombocytopenia (ITP, idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura) is an acquired thrombocytopenia caused by anti-platelet antibodies. The diagnosis of ITP may be challenging due to the various potential causes of thrombocytopenia, some of which are overlooked. Immunodeficiencies are also a rare cause of ITP. Although autoimmunity and, therefore, ITP are a common complication in primary immunodeficiency (PI) patients, there are not many publications in the literature that examine the frequency of PI in ITP patients and the immune abnormalities in these patients. Materials and Methods: Forty-five patients with ITP (F: 37 [78.7%], M: 10 [21.3%]) were included in the study (age 42.9 ± 15.9). Results: At least one antibody deficiency was detected in 7 patients (14.9%), and following further investigations, 2 patients (4.3%) were diagnosed with CVID, 3 (6.4%) with IgG deficiency, 1 (2.1%) with selective IgA deficiency and 1 (2.1%) with possible IgM deficiency. Immunoglobulin levels were normal while at least one abnormality was detected in 20 patients (42.6%) in peripheral lymphocyte subset analyses. The most common abnormality in this patient group was a reduced percentage of CD4+ T-cells (9 patients, 45% of patients with PLS abnormalities, 19.1% of all patients). CD3+ T-cell rates in 8 patients (17.8%), CD19+ B-cell rates in 6 (12.8%), CD3-CD16+56+ natural killer cell rates in 4 (8.5%), and CD4/CD8 cell ratios in 7 (14.9%) were reduced. In addition, the CD8+ T-cell rate in 8 patients (17%) was above the reference ranges. Conclusion: Adult patients who are diagnosed with ITP may develop a variety of immunological abnormalities in addition to hypogammaglobulinemia. Therefore, clinicians should not overlook immunological evaluation in the etiological investigation of ITP and should closely monitor patients with immunological abnormalities.
T-cell Imbalance or Decreased Th:Tc Ratio in Immune Thrombocytopenia: Is it Clinically Significant
2023
Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by low platelet count and various contributing factor. The imbalance in T cells may also cause ITP. Therefore, the present study was planned to assess the role of T-cells in pathogenesis of ITP and also to evaluate any possible link of Th:Tc imbalance to disease severity. Methods: The present study was conducted with 111 patients of ITP and similar number of controls as case control study with 1:1 ratio of from January 2017 to July 2019. The patients were grouped according to the guideline of ASH as newly diagnosed/persistent ITP(ND-ITP/P-ITP) and chronic/refractory ITP(C-ITP/R-ITP).The blood samples were obtained, and CBC parameters were observed using advanced hematology analyzer XN-1000.The T cells subset analysis was evaluated by BD FACS Calibur flow cytometer. The Fisher exact test was done to evaluated the difference among the groups with (p=<0.05) by using SPSS version 19. Results: Significantly reduced levels of hemoglobin, platelet counts with elevated IPF were observed in ND-ITP/P-ITP and C-ITP/R-ITP patients (p=<0.001).The significantly low Th:Tc ratio (p=<0.001) predicts imbalance of T cells in ND-ITP/P-ITP (0.86±0.47) as compared to control group (1.73±0.46).The mean of 0.84±0.34 Th:Tc ratio was observed in C-ITP/R-ITP children with ≤16 years. An insignificant difference (p= 0.89) was linked between children with non-severe chronic (0.84±0.42), severe chronic (0.82±0.49) and refractory ITP (0.85±0.51). Conclusion: In ITP patients' low levels of Th:Tc ratio was observed suggesting dysregulation of immune system. The chronicity of the disease may be linked to elevated production of Tc in children (≤16 years) with C-ITP/R-ITP.
Doc 2 .(ITP) disease in light of advances in Immunology.doc
Abstract The mechanism of ITP historically has been linking to platelet autoantibody emission and an outcome of platelet destruction. Recent research reveals a multifactorial pathogenesis. Over the past decade, an immune process in autoimmunity has been established by identifying and depicting of immunoregulatory cell trafficking and elements. As a result, there is an understanding of an interplay of both cellular and humoral immune behavior in breaking down of self-tolerance thus a recognition of the destruction of platelets present in ITP to bring about a future attack by advancements in therapy. Failure of bone marrow implies a vital role towards ITP thrombocytopenia. In managing ITP, there are treatment tactics that aim at thrombopoietin receptor thus increase the level of platelet production. The activity incurs a cost efficient design.
A Retrospective Observational Single-Centre Study on the Burden of Immune Thrombocytopenia (ITP)
Onkologie, 2012
Hintergrund: Deutsche Daten zu den ökonomischen Kon sequenzen der Immunthrombozytopenie (ITP) fehlen weit gehend. Patienten und Methoden: Eine retrospektive Be obachtungsstudie anhand der Krankenakten erwachsener Patienten mit gesicherter ITPDiagnose wurde an einer deutschen Universitätsklinik durchgeführt. Die Kostendar stellung erfolgte aus der Krankenhausperspektive. Ergebnisse: Von 50 auswertbaren Patienten konnten 45 nach der Krankheitsdauer klassifiziert werden: 19 Patienten < 3 Mo nate (38%, neu diagnostizierte ITP), 7 Patienten ≥ 3 bis < 12 Monate (14% persistierende ITP), 19 Patienten ≥ 12 Monate (38%, chronische ITP). Komplikationen umfassten 85 Blu tungsereignisse bei 43 Patienten, einschließlich dreier intra kranieller Blutungen. Dokumentiert wurden 955 ambulante Arztbesuche bei 43 (86%) und 92 Krankenhauseinweisungen bei 45 Patienten (90%). Von 46 behandelten Patienten (92%) erhielten alle Kortikosteroide, 25 (50%) intravenöse Immun globuline und 7 (14%) weitere Therapien. 12 Patienten (24%) wurden splenektomiert. Die durchschnittlichen direkten me dizinischen Gesamtkosten (Mittelwert (Standardabwei chung)) betrugen € 17 091 (€ 18 859) pro Patient, € 12 749 (€ 11 663) bei 17 neu diagnostizierten ITPPatienten mit 0,88 Monaten (0,65 Monate) durchschnittlicher Krankheits dauer und € 29 868 (€29 397) bei 13 Patienten mit chro nischer ITP mit 33,5 Monaten (16,8 Monate) durchschnittli cher Krankheitsdauer. Hauptkostentreiber waren Kranken haus auf enthalte. Schlussfolgerungen: Diese Daten über die gegen wärtige Gesundheitsversorgung von ITPPatienten in Deutschland zeigen einen erheblichen Ressourcenver brauch und unterstreichen daher die Notwendigkeit effek tiverer Behandlungsoptionen für einzelne Patienten.
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.
Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity. To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age-and sexmatched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and glucocorticoid induced tumor necrosis factor receptor (GITR) were also assessed by quantitative Real-time polymerase chain reaction TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and Transforming growth factor beta (TGF-β) were also measured.Results showed that the frequency of Tregs and the mean fluorescence intensity of forkhead box P3 (FOXP3) protein significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction in relative expression of both CTLA-4 and GITR mRNA in ITP patients (p=0.02 and p=0.006, respectively). The suppressive function of Tregs also diminished in ITP patients compared to controls. Both IL-10 and TGF-β cytokines were produced in lower amounts in ITP patients than controls. It could be concluded that alteration in Treg frequency and functional characteristics might be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients.
Annals of Hematology, 1996
In chronic idiopathic thrombocytopenic purpura (ITP) platelet destruction is caused by antibodies directed against plate][et membrane glycoproteins (GP), and the predominant autoantigens are known to be GPIb/IX and GPIIb/IIIa. In a recent study we reported that these antibodies frequently had a restricted light chain phenotype, thereby supporting a clonal origin. Similar findings and the presence of clonal B-cell populations in immune thrombocytopenias have been reported by others. In the present study we further explored the hypothesis of clonal B-cell expansions in chronic ITP. Twenty patients with chronic ITP were investigated. Antibodies were detected with an ELISA (MAIPA) specific for GPIb/IX and GPIIb/IIIa; circulating clonal B lymphocytes were assessed by flow-cytometric (FACS) clonal-excess analysis and by analyzing Ig-gene rearrangements (CDR3) with the PCR technique. Nine patients displayed a GP-specific antibody restricted to either kappa or lambda phenotype. However, FACS analysis and Ig-gene rearrangement studies did not disclose any circulating clonal B-cell population. Considering the sensitivity of the FACS analysis and Ig-gene rearrangement for detection of clonal B-cell populations, the hypothesis of clonally derived autoantibodies in ITP is still valid. Most probably, the clonal B-cell expansion responsible for the production of autoantibodies in ITP, if present, is below the detection limit for the techniques employed.