Profiles of Th1, Th2, Th17 and Treg Cells in Patients with Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3404-3404
Author(s):  
Rong-Fu Zhou ◽  
Jian Ou-yang ◽  
Da-Yu Chang ◽  
Jing-Yan Xu ◽  
Bing Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Treg Cells ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Active Stage ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Ifn Γ

Abstract Objective: To explore the profiles of Th1,Th2, Th17 and Treg cells in patients with chronic idiopathic thrombocytopenic purpura. Methods: Samples of peripheral blood were collected from 30 chronic ITP patients ( 9 males and 21 females), aged 41, 21 being in active stage, and 9 in remission stage, and 9 healthy persons in control (3 males and 6 females), aged 36. Peripheral blood was cultured, and activated with PMA/ionomycin when Th1, Th2 and Th17 cells were detected. Flow cytometry was used to measure the intracellular cytokines interferon (IFN)-γ, interleukin (IL)-4 and interleukin (IL)-17 so as to identify the Th1 cells (CD3+ CD8− IFN-γ+ IL-4− cells), Th2 cells (CD3+ CD8− IFN-γ − IL-4+ cells) and IL-17 cells (CD3+ CD8− IL-17+ cells); Treg cells were identified to CD4+ CD25+ Foxp3+ cells and uncultured peripheral blood was used to measured the CD4+ CD25+ Foxp3+ cells by flow cytometry. The ratios of Th1/Th2 were calculated. Results: The Th1/Th2 ratio for patients in active stage was 15.04±9.67, significantly higher than those for patients in remission stage (7.17±5.38, P <0.05) and in control (8.47±3.78, P <0.05); the percentage of Treg cells of the patients in active stage was 0.89±0.58%, significantly decreased than those of patients in remission stage (6.41±1.86%, P <0.001) and in control (6.06±0.85%, P <0.001); the percentage of Th17 cells was 1.94±0.77% for patients in active stage, 2.16±0.52% for patients in remission stage and 1.82±0.58% for patients in control, respectively, and there was no statistic significance between them. Conclusion: Chronic ITP is a Th1 predominant disease; decreased number and function of Treg cells might be one of mechanisms that cause immune regulation dysfunction in chronic ITP; Th17 cells might not play a role in the development of chronic ITP.

scholarly journals Therapy of chronic idiopathic thrombocytopenic purpura in adults [see comments]

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2309-2317 ◽  
Author(s):  
P Berchtold ◽  
R McMillan
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Clinical Studies ◽  
Morbidity And Mortality ◽  
Cooperative Group ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Therapeutic Approaches ◽  
Group Setting ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Large Numbers

Abstract Chronic ITP is a common hematologic illness. Approximately three fourths of the patients respond to corticosteroids or splenectomy and need no further treatment. Patients refractory to these two therapeutic approaches are relatively resistant to present forms of treatment and are at much greater risk for morbidity and mortality. Future clinical studies evaluating therapy in this refractory group would be best performed in a cooperative group setting in which large numbers of patients could be treated in a prospective randomized manner.

Chronic idiopathic thrombocytopenic purpura (ITP): molecular mechanisms and implications for therapy

2004 ◽  
Vol 6 (24) ◽  
pp. 1-17 ◽  
Author(s):  
Per-Ola Andersson ◽  
Hans Wadenvik
Keyword(s):  
T Cells ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Molecular Mechanisms ◽  
Reticuloendothelial System ◽  
Current Status ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Humoral Immune ◽  
Chronic Itp ◽  
Relative Contribution

Chronic idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder in which platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies. However, it is becoming clear that the pivotal process of the humoral immune response in the pathogenesis of the disorder is a complex interaction between antigen-presenting cells, T cells and B cells. Furthermore, it is increasingly evident that regulatory T cells play an important role and that T-cell-mediated cytotoxicity contributes to the destruction of platelets in ITP. Different new approaches to immunotherapy in chronic ITP have been explored, including use of anti-CD20, anti-CD154 and anti-CD52 antibodies. So far, these therapies have been antigen-nonspecific and the risk of general immunosuppression is a concern. Thus, improving our understanding of the interaction and relative contribution of humoral and cell-mediated mechanisms is essential for developing antigen-specific immunotherapies for the treatment of this disorder. This review aims to elucidate the current status of knowledge of the cellular and humoral immune components of chronic ITP, together with the implications of this knowledge for therapy.

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 952-957 ◽  
Author(s):  
Roberto Stasi ◽  
Adalberto Pagano ◽  
Elisa Stipa ◽  
Sergio Amadori
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Count ◽  
Side Effects ◽  
Partial Response ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Antibody Treatment ◽  
Minor Response ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp

The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m2 once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 × 109/L) was observed in 5 cases, a partial response (platelet count between 50 and 100 × 109/L) in 5 cases, and a minor response (platelet count below 50 × 109/L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted.

Abstract 171: Acute Sagittal Sinus Thrombosis in an Elderly Patient with Chronic Idiopathic Thrombocytopenic Purpura

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Huimin Wu ◽  
Robert Paulino ◽  
Qi Shi ◽  
Sandhya Samavedam ◽  
Indupriya Pallekonda ◽  
...  
Keyword(s):  
Platelet Count ◽  
Venous Thrombosis ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Sinus Thrombosis ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Sagittal Sinus ◽  
History Of

INTRODUCTION Chronic idiopathic thrombocytopenic purpura (ITP) is classified as a bleeding disorder that involves autoimmune platelet destruction. Cerebral venous sinus thrombosis in association with chronic ITP is rarely reported in medical literature. CASE PRESENTATION A 70-year-old female with a history of chronic ITP, on prednisone, and coronary artery disease presented with a four-day history of vomiting and diarrhea. Platelet count at the time of admission was 25×10 9 /L. She was treated with i.v normal saline. Platelets fell to 12×10 9 /L and intravenous immunoglobulin (IVIG) was started. Six days later, the patient developed confusion and right sided weakness. Repeat platelet count was 13x10 9 /L. MRI of the brain showed bilateral cortical infarcts suggesting sagittal vein involvement. MRV confirmed thrombosis of the posterior portion of the sagittal sinus. Bone marrow aspirates and core biopsy done to rule out other hematological disorders showed tri-lineage hematopoiesis with adequate marrow megakaryocytes. Hypercoagulable work up was unremarkable. ITP was treated with rituximab and romiplostim. Repeat MRV after 2 weeks showed no new thrombosis or hemorrhage. DISCUSSION ITP is occasionally associated with venous thrombosis. The paradoxical occurrence of venous thrombosis in the setting of ITP is poorly understood. Previous data postulates that platelet destruction releases humoral factors and microparticles, which may increase thrombotic events by the activation of thrombin and other coagulation factors. Other possible mechanisms include endothelial damage by autoantibodies directed against antigens on platelets and endothelial cells. More recently, reports have described IVIG-induced arterial and venous thrombotic complications. Treatment of thrombosis in the setting of ITP is complex and requires in-depth risk/benefit assessment. Our case highlights the dilemma of stroke treatment and prevention predicated on antiplatelet therapies for patients with ITP. Additional studies on chronic ITP associated with thrombosis are needed to establish preventive and treatment guidelines.

Bone Marrow Effects of High Dose Folic Acid Therapy in Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4016-4016
Author(s):  
Elizabeth Schulz ◽  
Rosangela Albuquerque Ribeiro Holanda ◽  
Francisco Dario Rocha Filho ◽  
Guilherme Alves de Lima Henn ◽  
Ricardo Alves Oliveira
Keyword(s):  
Bone Marrow ◽  
Folic Acid ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
High Dose ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Bone Marrow Biopsies ◽  
Platelet Counts ◽  
Marrow Cellularity

Abstract Chronic idiopathic thrombocytopenic purpura (CITP) is an autoimmune disorder characterized by the production of autoantibodies against specific platelet antigens and characterized by low platelet counts in peripheral blood over a period of at least 6 months. Corticosteroids have been generally used as first line therapy with serious side effects. Previously, we described the beneficial effect of high dose folic acid (HDFA), 5 to 20 mg PO daily), in the therapy of this disease. Presently, we report the treatment of two patients with severe thrombocytopenia with HDFA. A 46 year old splenectomized woman (P1) and a 32 year old non-splenectomized man (P2), who were moderately refractory to prednisone and prednisolone, had a previous history of undifferentiated connective tissue disease characterized by one episode of arthritis (P2 with a positive rheumatoid factor and morning stiffness). Both patients had normal serum folic acid and vitamin B12, and no signs of megaloblastic or dysplastic alterations were evidenced in bone marrow aspirates. Ham test was negative and CD55/CD59 values for both patients were equal to normal controls. Bone marrow biopsies were also performed prior to the treatment with folic acid (FA) to evidence a global decrease in bone marrow cellularity (30% in case 1 and 20% in case 2). Concomitant infections or other diseases were excluded. Prednisone was tapered slowly, and high dose folic acid administration was initiated at this time. P1 achieved complete remission (CR) in 5 months with slowly tapering of folic acid during one year, remaining with normal platelet counts after one more year with no treatment. P2 achieved sustained partial remission (PR) with platelet counts ranging 63 x 109L to 113 x109/L. Interestingly, sequential bone marrow biopsies performed 2 years after the beginning of HDFA therapy revealed a marrow cellularity of 50% and 35% for P1 and P2, respectively. We demonstrated that the successful CR and PR to HDFA are associated with a significant increase in the overall bone marrow cellularity in both cases (20% in P1 and 15% in P2). Apoptotic features in idiopathic thrombocytopenic purpura (ITP) were characterized by Houwerzijl et al who demonstrated apoptosis and para-apoptosis as ultrastructural alterations in bone marrow megacaryocytes, supportive of ineffective thrombopoiesis as an underlying phenomenon in this study. Buemi et al demonstrated that addition of folic acid to the medium of vascular smooth muscle cells in culture inhibited the percentage of apoptotic and necrotic cells through a decrease in homocysteine concentration. The exact mechanism through which high dose folic acid is able to increase platelets measured in peripheral blood of patients with ITP and induce sustained CR and PR is so far unknown and remains to be explained. However, the present response to HDFA suggest a qualitative and especially quantitative role for this drug in protecting and upgrading the hematopoietic bone marrow and, consequently, restoring the platelet production in these 2 patients.

Elevated Expression of IL-17 and IL-23 in Patients with Immune Thrombocytopenic Purpura

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4537-4537
Author(s):  
Feng Li ◽  
Shanhua Zou ◽  
Yunfeng Cheng
Keyword(s):  
T Cells ◽  
Immune Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Statistical Difference ◽  
Plasma Concentrations ◽  
Healthy Controls ◽  
Cd4 Cells ◽  
Thrombocytopenic Purpura ◽  
Ifn Γ

Abstract Introduction: In conjunction with IL-6 and TGF-β, IL-23 stimulates naïve CD4+ T cells to differentiate into Th17 cells. Th17 cells produce IL-17, a pro-inflammatory cytokine that play an important role in the pathogenesis of several autoimmune disorders. However, to date, the role of Th17 cells in immune thrombocytopenic purpura (ITP), a type of autoimmune diseases, has not been clearly established yet. Methods: Peripheral bloods were obtained from 10 patients with ITP at onset, in remission and from 15 healthy control subjects. The frequencies of IL-17 producing T cells in peripheral blood were analyzed by flow cytometry. Peripheral blood Mononuclear cells (PBMCs) were isolated using Ficoll density-gradient centrifugation and the CD4+ cells were separated by immuno-magnetic microbeads selection. Plasma concentrations of Th17 cell-associated cytokines such as IL-12, IL-17, IL-23, IFN-γ, IL-6 and TGF-β were measured using ELISA. The mRNA expression levels of IL-17, IL-12p40, IFN-γ, IL-23p19 in CD4+ cells were determined by Real-Time PCR. Results: The frequencies of IL-17-producing T cells were significantly increased in ITP patients at onset, compared to ITP patients in remission (10.7±5.5 % vs 4.1±3.5 %, p &lt; 0.05) and healthy controls (10.7±5.5 % vs 2.1±1.6 %, p &lt; 0.05), however there was no statistical difference between ITP patients in remission and healthy controls. Comparing to healthy subjects, the plasma concentrations of IL-12 (33.3±15.25 pg/ ml vs 12.8±7.24 pg/ml, p&lt;0.05), IL-17 (37.3±12.1 pg/ml vs 5.1±3.6 pg/ml, p &lt; 0.05), IL-23 (30.01±9.33 pg/ml vs 10.42±13.19 pg/ml, p &lt; 0.05) in patients with ITP at onset were found significantly elevated whereas no statistical difference was observed for the levels of IL-12, IL-17 and IL-23 between ITP patients in remission and healthy controls. Furthermore, the expression levels of IL-23p19 mRNA were significantly increased in ITP patients at onset, compared to healthy controls. Changes in IL-23p19 mRNA expression and IL-17 were strongly correlated (R = 0.66, p &lt; 0.05). Conclusion: Our results support the hypothesis that Th17 cells are involved in the development of ITP and Th17 cells could potentially constitute a novel therapeutic target.

scholarly journals Abnormal platelet function and arachidonate metabolism in chronic idiopathic thrombocytopenic purpura

Blood ◽  
1981 ◽  
Vol 58 (2) ◽  
pp. 326-329 ◽  
Author(s):  
MJ Stuart ◽  
JG Kelton ◽  
JB Allen
Keyword(s):  
Platelet Aggregation ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Platelet Function ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Arachidonate Metabolism

Abstract We observed several patients with chronic idiopathic thrombocytopenic purpura (ITP) whose bleeding times were more prolonged than would have been expected from their platelet counts. To investigate this further, we performed in vivo and in vitro platelet function studies, assessed arachidonate metabolism, and measured platelet-associated IgG (PAIGG) in seven patients with chronic ITP. The bleeding times of three of the patients were prolonged for greater than 7 min, and all of these patients had impaired platelet aggregation and abnormal platelet arachidonic acid metabolism as reflected by increased production of the lipoxygenase product HETE and a concomitant decrease in cyclooxygenase products, TXB2 and HHT (p less than 0.001). The abnormalities noted were not due to concomitant drug ingestion, since they were present on repeated evaluation. There was no relationship between the platelet count and the bleeding time; however, there was a significant inverse correlation between the bleeding time and TXB2 production in all patients evaluated (r = 0.81; p less than 0.05). There was no relationship between the level of platelet-associated IgG and any parameter of platelet aggregation or arachidonate metabolism. The abnormalities noted should be looked for in the individual patient with chronic ITP, since the bleeding tendency is exacerbated by the superimposed impairment of platelet function even at platelet counts of greater than 50,000/cu mm, levels generally regarded as “safe”.

scholarly journals Structural Changes in the Platelets as Observed by Electron Microscopy

Blood ◽  
1954 ◽  
Vol 9 (6) ◽  
pp. 595-601 ◽  
Author(s):  
H. BRAUNSTEINER ◽  
K. FELLINGER ◽  
F. PAKESCH
Keyword(s):  
Electron Microscopy ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Structural Changes ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp

Abstract Deficient pseudopod formation and spreading of platelets on Formvar films were encountered in cases of chronic idiopathic thrombocytopenic purpura and thrombocytoasthenias. The same defect together with agglutination was induced in isolated normal platelets by a platelet agglutinin from the serum of one case of chronic ITP. The possible significance of these results is briefly discussed.

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