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Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents.

ABSTRACT: Immune thrombocytopenia (ITP) is an autoantibody-mediated bleeding disorder with both accelerated platelet destruction and impaired platelet production. We and others have described impaired regulatory CD4(+)CD25(hi) T cells (Treg) numbers and/or suppressive function in ITP patients. Clinical trials using thrombopoietic agents to stimulate platelet production have shown favorable outcomes in ITP patients, but information on the immunologic responses of treated patients are lacking. We studied the immunologic profile of chronic ITP patients before (n = 10) and during treatment with thrombopoietin receptor (TPO-R) agonists (n = 9). Treg activity, as measured by suppression of proliferation of autologous CD4(+) CD25(-) cells, was improved in patients on treatment (P < .05), and the improvement correlated with reduction in interleukin-2-producing CD4(+) cells, consistent with dampening of immune responses. There was a concomitant increase in total circulating transforming growth factor-?1 (TGF-?1) levels (P = .002) in patients on treatment, and the levels of TGF-?1 correlated with the degree of improvement in platelet counts (r = .8, P = .0002). This suggests that platelets in patients on TPO-R treatment may play a role in improving Treg function, either directly or indirectly by enhanced release of TGF-?1 as a result of greater platelet turnover. In conclusion, our findings suggest that thrombopoietic agents in patients with ITP have profound effects to restore immune tolerance.

SUBMITTER: Bao W

PROVIDER: S-EPMC2996119 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents.

Bao Weili W Bussel James B JB Heck Susanne S He Wu W Karpoff Marissa M Boulad Nayla N Yazdanbakhsh Karina K

Blood 20100805 22

Immune thrombocytopenia (ITP) is an autoantibody-mediated bleeding disorder with both accelerated platelet destruction and impaired platelet production. We and others have described impaired regulatory CD4(+)CD25(hi) T cells (Treg) numbers and/or suppressive function in ITP patients. Clinical trials using thrombopoietic agents to stimulate platelet production have shown favorable outcomes in ITP patients, but information on the immunologic responses of treated patients are lacking. We studied th ...[more]

PMID: 20688957

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Project description:Chronic immune thrombocytopenia (ITP) is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy.This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP.A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress), and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS), intravenous immunoglobulin (IVIg), anti-D immunoglobulin (anti-D), rituximab (RT), and splenectomy (SPL), as well as for other patient-referenced therapies (captured as "other").The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71), and 68% reported a typical low platelet count of < 50,000/?L. Current or past treatment with CS was reported by 92% (n = 542) of patients, 56% (n = 322) for IVIg, 36% (n = 209) for anti-D, 36% (n = 213) for RT, and 39% (n = 227) for SPL. A substantial proportion of CS-treated patients reported side effects (98%, P < 0.05), were highly bothered by their side effects (53.1%, P < 0.05), and reported the need to stop or reduce treatment due to side effects (37.8%, P < 0.05). Among patients reporting side effects of treatment, significant associations were noted for the number of side effects, aggregate bother of reported side effects, and the need to stop or reduce treatment (all P < 0.05).Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.

Project description:BackgroundImmune checkpoint inhibitors (ICIs), an enormous oncological breakthrough in the last 10 years, have become the standard treatments for several types of solid cancers. Although ICIs are generally well tolerated and result in favorable outcomes, they also cause unique immune-related adverse events (irAEs) across bodily systems and organs. Compared to most common irAEs, which occur in the endocrine, skin, pulmonary system, and gastrointestinal tract, haematological irAEs (haem-irAEs) are relatively rare but potentially life-threatening events that are occasionally irreversible and refractory. Currently, haem-irAEs are not sufficiently understood, management, and lack consensus, while other common irAEs have well been characterized and managed. The reports of ICI-related thrombocytopenia in small cell lung cancer (SCLC) are rarely seen. Hence, we reported a rare case of severe steriod-resistant ICI-related thrombocytopenia after received chemotherapy plus anti-PD-L1 inhibitor in SCLC patient. Our case exemplifies the diagnosis, diagnosis of exclusion, treatment, and prognosis of thrombocytopenia in the pattern of combination therapy, meanwhile, the subject of diagnosis, therapies, therapeutic strategies for refractory type and incidence, potential biomarkers, mechanisms and prognosis in ICI-related thrombocytopenia have been fully discussed.Case descriptionHerein, we present a 64-year-old man diagnosed advanced SCLC developed refractory immune-related severe thrombocytopenia, who achieved favorable outcomes of cancer following chemotherapy combined with atezolizumab administrated. Routine blood re-examination on the third day of 6th therapy showed a thrombocyte count of 11×109/L. Combined the medical history and the results of laboratory tests, the diagnosis of ICI-induced thrombocytopenia was confirmed. Despite large doses of methylprednisolone, immunoglobulin, and rituximab, intermittent platelet transfusion, thrombopoietin being administrated to the patient, there were no signs of platelet count and hemoglobin improvement. Currently, this is the first case about atezolizumab induced thrombocytopenia in SCLC patient, while there is extremely rare haem-irAEs reported in SCLC.ConclusionsAlthough ICI-related severe thrombocytopenia is rare, it may persist or even be fatal. Clinicians should pay more attention to its diagnosis and prompt treatment. Once developed thrombocytopenia, large doses of methylprednisolone, ntermittent platelet transfusion, thrombopoietin should be timely administrated, also plasma exchange or rilzabrutinib, other immunosuppressive drugs, or IL-6 inhibitor warrant apply if steriod-resistant.

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Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents.

Publications

Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents.

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