Abstract
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which, via unresolved mechanisms, platelets and megakaryocytes (MKs) are targeted by autoantibodies and/or T cells resulting in increased platelet destruction and impairment of MK function. Over the years, several therapeutic modalities have become available for ITP, however, therapeutic management has proven to be very challenging in several cases. Patients refractory to treatment can develop a clinically worsening disease course, treatment-induced toxicities and are predisposed to development of potentially life-endangering bleedings. It is therefore of critical importance to timely identify potential refractory patients, for which novel diagnostic approaches are urgently needed in order to monitor and predict specific therapeutic responses. In this paper, we propose promising diagnostic investigations into immune functions and characteristics in ITP, which may potentially be exploited to help predict platelet count responses and thereby distinguish therapeutic responders from non-responders. This importantly includes analysis of T cell homeostasis, which generally appears to be disturbed in ITP due to decreased and/or dysfunctional T regulatory cells (Tregs) leading to loss of immune tolerance and initiation/perpetuation of ITP, and this may be normalized by several therapeutic modalities. Additional avenues to explore in possible prediction of therapeutic responses include examination of platelet surface sialic acids, platelet apoptosis, monocyte surface markers, B regulatory cells and platelet microparticles. Initial studies have started evaluating these markers in relation to response to various treatments including glucocorticosteroids (GCs), intravenous immunoglobulins (IVIg) and/or thrombopoietin receptor agonists (TPO-RA), however, further studies are highly warranted. The systematic molecular analysis of a broad panel of immune functions may ultimately help guide and improve personalized therapeutic management in ITP.
Highlights
This article is an open access articleImmune thrombocytopenia (ITP) is an acquired hematological autoimmune bleeding disorder characterized by an isolated thrombocytopenia and may clinically present as petechiae, purpura, mucosal bleedings, intracranial hemorrhages (~0.2% of the cases), with a reduced health-related quality of life (HRQoL) [1]
A survey of several studies suggests that almost two-thirds of patients have at least a partial immediate response to corticosteroids and three-quarters have some response to intravenous immunoglobulin (IVIg) or anti-D [4]
We hypothesize that immune functions and characteristics of platelets are likely impaired in ITP, and alterations in these markers induced by therapies in ITP may be exploited for the design of novel diagnostic approaches which may help predict responders and non-responders to specific treatment modalities
Summary
Immune thrombocytopenia (ITP) is an acquired hematological autoimmune bleeding disorder characterized by an isolated thrombocytopenia It has been estimated that approximately 40–60% of newly diagnosed adult ITP patients have a sustained response to initial treatment with standard first-line therapies (standard-dose corticosteroids, IVIg, anti-D) after 6 months [5]. A quarter of adults with newly diagnosed ITP, remains relapse-free beyond one year [5] These results on long term response rates to first-line therapy show a high variability of 8–43% which may reflect the differences in ITP patient population, duration and dose of treatment and in definitions of platelet response. Identification of refractory patients is of critical importance, for which novel diagnostic tools that can monitor and predict therapeutic responses to specific treatment modalities are highly warranted Recent insights into this will be discussed in the current paper, and how they may serve as a much-needed stepping stone for the development of novel diagnostic assays which may aid in managing treatment approaches in ITP
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