Imbalanced immune homeostasis in immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders.

Platelet‐specific antibodies and differences in their expression in childhood immune thrombocytopenic purpura predicts clinical progression

“…ITP is an antibody‐mediated destructive disease, and autoreactive antibodies that target platelet antigen complexes are considered responsible for the accelerated destruction of platelets by the reticuloendothelial system and for the inhibition of megakaryopoiesis, in which platelet glycoprotein GPIIb/IIIa and GPIb/IX are the two most frequently targeted autoantigens . Studies on adult affect clinical prognosis and that the presence of anti‐GPIb/IX autoantibodies is a predictive factor for poor prognosis risk .…”

Intravenous immunoglobulin treatment of spleen cells from patients with immune thrombocytopenia significantly increases the percentage of myeloid‐derived suppressor cells

“…During the last decade, MDSCs have emerged as key regulatory cells in the context of tumour growth, inflammation, transplantation and autoimmunity (Gabrilovich & Nagaraj, ; Cripps & Gorham, ; Greten et al , ; Fujii et al , ), and MDSC number and function are reduced in patients with ITP (Hou et al , ). MDSCs may play a decisive role in the immunological pathogenesis of human ITP because a defect in these regulators of adoptive immunity may augment T‐lymphocyte‐mediated destruction of platelets in concert with reduced T‐regulatory cells (Hou et al , ; Yazdanbakhsh, ) and increased B‐regulatory cells (Aslam et al , ). These data are consistent with the finding that high‐dose dexamethasone increases the number and function of MDSCs in patients with ITP (Hou et al , ).…”

<p>Romiplostim for the Treatment of Immune Thrombocytopenia: Spotlight on Patient Acceptability and Ease of Use</p>

“…2 Cell-mediated platelet destruction and disruption of T cell homeostasis are also well described. [2][3][4][5] ITP is also characterized by impaired platelet production secondary to antibody effect in the bone marrow and subsequent megakaryocyte ultrastructural abnormalities. 6 Primary ITP occurs in the absence of a condition driving immune dysregulation, whereas secondary ITP defines the presence of an associated condition such as hepatitis C, systemic lupus erythematosus, or common variable immunodeficiency.…”