Dataset Information

Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-? receptor polymorphisms.

ABSTRACT: In childhood immune thrombocytopenia (ITP), anti-platelet autoantibodies mediate platelet clearance through Fc-? receptor (Fc?R)-bearing phagocytes. In 75% to 90% of patients, the disease has a transient, self-limiting character. Here we characterized how polymorphisms of Fc?R genes affect disease susceptibility, response to intravenous immunoglobulin (IVIg) treatment, and long-term recovery from childhood ITP. Genotyping of the FCGR2/3 locus was performed in 180 children with newly diagnosed ITP, 22 children with chronic ITP, and 180 healthy control children by multiplex ligation-dependent probe amplification. Children with newly diagnosed ITP were randomly assigned to a single administration of IVIg or observation, and followed for 1 year (Treatment With or Without IVIg for Kids With ITP [TIKI] trial). We defined transient ITP as a complete recovery (?100 × 109/L) 3 months after diagnosis, including both self-limiting disease/IVIg responders and chronic ITP as absence of a complete recovery at 12 months. ITP susceptibility, as well as spontaneous recovery and response to IVIg, was associated with the genetic variants FCGR2C*ORF and FCGR2A*27W and the FCGR2B promoter variant 2B.4. These variants were overrepresented in patients with transient (N = 131), but not chronic (N = 43), disease. The presence of FCGR2C*ORF predisposed to transient ITP with an odds ratio of 4.7 (95% confidence interval, 1.9-14.3). Chronic ITP was associated with a deletion of FCGR2C/FCGR3B (copy number region 1) with an odds ratio of 6.2 (95% confidence interval, 1.8-24.7). Taken together, susceptibility to transient and chronic ITP is distinctly affected by polymorphic variants of FCGR2/3 genes. Our data suggest that genotyping of the FCGR2/3 locus may be useful for prognosis and guidance of treatment decisions in newly diagnosed childhood ITP.

SUBMITTER: Schmidt DE

PROVIDER: S-EPMC6616256 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms.

Schmidt David E DE Heitink-Pollé Katja M J KMJ Laarhoven Annemieke G AG Bruin Marrie C A MCA Veldhuisen Barbera B Nagelkerke Sietse Q SQ Kuijpers Taco W TW Porcelijn Leendert L van der Schoot C Ellen CE Vidarsson Gestur G de Haas Masja M

Blood advances 20190701 13

In childhood immune thrombocytopenia (ITP), anti-platelet autoantibodies mediate platelet clearance through Fc-γ receptor (FcγR)-bearing phagocytes. In 75% to 90% of patients, the disease has a transient, self-limiting character. Here we characterized how polymorphisms of FcγR genes affect disease susceptibility, response to intravenous immunoglobulin (IVIg) treatment, and long-term recovery from childhood ITP. Genotyping of the <i>FCGR2/3</i> locus was performed in 180 children with newly diagn ...[more]

PMID: 31270082

Similar Datasets

Project description:Essentials There is a need for improved tools to predict persistent and chronic immune thrombocytopenia (ITP). We developed and validated a clinical prediction model for recovery from newly diagnosed ITP. The Childhood ITP Recovery Score predicts transient vs. persistent ITP and response to intravenous immunoglobulins. The score may serve as a useful tool for clinicians to individualize patient care. ABSTRACT: Background Childhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most pronounced in children with persistent and chronic ITP. Clinical characteristics are associated with ITP outcomes, but there are no validated multivariate prediction models. Objective Development and external validatation of the Childhood ITP Recovery Score to predict transient versus persistent ITP in children with newly diagnosed ITP. Methods Patients with a diagnosis platelet count ≤ 20 × 109 /L and age below 16 years were included from two prospective multicenter studies (NOPHO ITP study, N = 377 [development cohort]; TIKI trial, N = 194 [external validation]). The primary outcome was transient ITP (complete recovery with platelets ≥100 × 109 /L 3 months after diagnosis) versus persistent ITP. Age, sex, mucosal bleeding, preceding infection/vaccination, insidious onset, and diagnosis platelet count were used as predictors. Results In external validation, the score predicted transient versus persistent ITP at 3 months follow-up with an area under the receiver operating characteristic curve of 0.71. In patients predicted to have a high chance of recovery, we observed 85%, 90%, and 95% recovered 3, 6, and 12 months after the diagnosis. For patients predicted to have a low chance of recovery, this was 32%, 46%, and 71%. The score also predicted cessation of bleeding symptoms and the response to intravenous immunoglobulins (IVIg). Conclusion The Childhood ITP Recovery Score predicts prognosis and may be useful to individualize clinical management. In future research, the additional predictive value of biomarkers can be compared to this score. A risk calculator is available (http://www.itprecoveryscore.org).

Project description:Childhood immune thrombocytopenia (ITP; platelet count < 100 × 109/L) is the most common bleeding disorder in children. A total of 3-5% of children with ITP face a greater risk of bleeding, resulting in significant morbidity and mortality. Childhood ITP is often benign and self-limited; however, children with severe ITP (platelet count < 30 × 109/L) require investigation and monitoring. In addition, 20% of ITP patients may not go into remission (platelet counts < 100 × 109/L by 12 months after diagnosis) and may develop chronic ITP. The early identifying predictors associated with the resolution of severe ITP at the time of diagnosis may be helpful for family guidance. However, there is still controversy about the associations between the clinical factors at the time of initial diagnosis and the definitions of disease remission assessed at different timepoints after diagnosis. This retrospective study aimed to analyze the shared clinical factors among the disease remission definitions at three arbitrarily set timepoints-3, 6, and 12 months after diagnosis. This study retrieved records for hospitalized children aged under 18 years and diagnosed with ITP from the hospital registry in a tertiary university hospital. Clinical variables were recorded by reviewing the medical records with structured data entry for ITP admission. The serial follow-up platelet counts within 12 months after diagnosis were recorded. The times of ITP remission were identified by experienced pediatric hematologists. Patients with mild-form ITP (platelet counts ≥ 30 × 109/L) at diagnosis or who were lost to follow-up within 3 months were excluded. From 1988 to 2019, 546 children were enrolled, and a total of 497 children with severe ITP were included in the further analysis. In total, one (0.2%) died of an intracranial hemorrhage, 363 (73.2%) children went into remission at 3 months, 40 (8.1%) went into remission between 6 and 12 months, and 104 (20.9%) developed chronic ITP. The shared significant predictors for remission by the third, sixth, and twelfth months included pre-adolescent age (<10 years) at diagnosis, abrupt onset (duration of symptoms prior to admission ≤ 2 weeks), and speedy recovery (platelet count > 100 × 109/L at 1 month post diagnosis). ITP patients with positive viral serology tests or vaccination within 4 weeks had trends of delayed remission. In conclusion, diagnosis before preadolescent age, abrupt onset, and speedy recovery may share favorable factors for the remission of childhood ITP assessed at different timepoints.

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.

Dataset Information

Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-? receptor polymorphisms.

Publications

Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-γ receptor polymorphisms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets