Potential Diagnostic Approaches for Prediction of Therapeutic Responses in Immune Thrombocytopenia

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.

Keywords: diagnostics; immune thrombocytopenia (ITP); therapeutic responses; therapy; therapy prediction.

Figure 1

Potential diagnostic approaches for assessment of therapeutic responses in ITP. Promising diagnostic approaches for prediction of platelet count responses and thereby distinguish therapeutic responders from non-responders are depicted: T cell homeostasis (D1), Platelet surface sialic acids (D2), Platelet apoptosis (D3), Monocyte surface markers (D4), B regulatory cells (D5) and Platelet microparticles (PMPs). Each approach indicates therapeutic non-response vs. response, with their effects (+ indicates a stimulatory effect and - an inhibitory effect) on the features of the ITP pathophysiology. So far, the initial preliminary evidence may support the involvement of the following therapeutic modalities in relation to the diagnostic approaches: (D1) glucocorticosteroids, high-dose dexamethasone, IVIg, low-dose decitabine, TPO-RA; (D2) Corticosteroids, IVIg, TPO-RA; (D3) IVIg; (D4) glucocorticosteroids; (D5) TPO-RA; (D6) Corticosteroids, TPO-RA. This figure was created with BioRender.com.