Predictive Value of High ICAM-1 Level for Poor Treatment Response to Low-Dose Decitabine in Adult Corticosteroid Resistant ITP Patients

Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. Endothelial cell activation/injury has been found in some autoimmune diseases including SLE, systemic sclerosis, and rheumatoid arthritis, but its role in ITP pathogenesis remains unclear. This study attempted to elucidate the correlation between endothelial dysfunction and disease severity of ITP and find related markers to predict response to low-dose decitabine treatment. Compared with healthy volunteers, higher plasma levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and Angiopoietin-2 were found in adult corticosteroid resistant ITP patients. Notably, ICAM-1 levels were negatively correlated with the platelet count, and positively associated with the bleeding score. Recently, we have reported the efficacy and safety of low-dose decitabine in adult patients with ITP who failed for the first line therapies. Here, we evaluated the correlation of plasma ICAM-1 level with the efficacy of low-dose decitabine therapy for corticosteroid resistant ITP. A total of 29 adult corticosteroid resistant ITP patients who received consecutive treatments of low-dose decitabine were enrolled in this study. Fourteen patients showed response (nine showed complete response and five showed partial response). The levels of ICAM-1 before and after treatment were significantly higher in the non-responsive ITP patients than in the responsive patients. As shown in the multivariable logistic regression model, the odds of developing no-response to low-dose decitabine increased by 36.8% for per 5 ng/ml increase in plasma ICAM-1 level [odds ratio (OR) 1.368, 95% confidence interval (CI): 1.060 to 1.764]. In summary, this was the first study to elucidate the relationship between endothelial dysfunction and corticosteroid resistant ITP and identify the potential predictive value of ICAM-1 level for response to low-dose decitabine.

Association of metformin treatment and outcome in adult patients with ITP and pre‐existing T2DM

“…Information, including demographic characteristics, clinical manifestations, bleeding scores, treatment and outcomes, were carefully recorded. Bleeding scores were rated according to the rating system for bleeding in ITP with slight modifications 1,20,21 . Information concerning age was excluded from the original scale in accordance with the protocol of different clinical bleeding systems.…”

“…Bleeding scores were rated according to the rating system for bleeding in ITP with slight modifications. 1,20,21 Information concerning age was excluded from the original scale in accordance with the protocol of different clinical bleeding systems. Our experienced research team carefully scanned, interpreted, and doublechecked the data to ensure accuracy.…”

Scoping Review on Epigenetic Mechanisms in Primary Immune Thrombocytopenia

“…A before-and-after treatment study done with thrombopoietin-receptor agonists (TPO-RA) (romiplostim and eltrombopag) has identified that miR-199a-5p and miR-221-3p can predict platelet response to TPO-RA-treatment before treatment [ 156 ]. Recent research has investigated decitabine as a treatment for ITP [ 157 , 158 ]. Decitabine is a demethylating agent that in low doses is reported to have three functions: (i) promote megakaryocyte maturation and platelet production through demethylating hypermethylated promoters of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene [ 159 ]; (ii) restores expression of programmed cell death protein 1 (PD-1), by demethylating hypermethylated PD-1 promoter in CD8+ T cells, which inhibits cytotoxic T lymphocytes (CTLs)-mediated platelet destruction [ 160 ] and (iii) enhances Tregs and restores the balance of T helper cell subtypes through inhibition of STAT3 activation which decreases STAT3 and AKT phosphorylation [ 160 ].…”

Current therapeutic strategies and perspectives in refractory ITP: What have we learned recently?

“…In the terms of endothelial function, bone marrow endothelial progenitor cells (BM EPCs) can improve hematopoiesis and megakaryocytopoiesis, and regulate thrombopoiesis ( 25 ). Correcting endothelial dysfunction added a promising tool to the treatment armory of corticosteroid-resistant ITP ( 26 ). Regarding the mechanism of IVIG treatment for ITP, interleukin (IL)-11 serves as a stimulating factor to increase platelets and other haemostasis factors (VWF and FVIII), which indicates that recombinant IL-11 (rIL-11) may be a promising substitute for IVIG ( 27 ).…”

“…Researchers first found endothelial cell alterations in a canine ITP model ( 112 ). Subsequently, it was found that corticosteroid-resistant ITP patients had endothelial dysfunction ( 26 ). Targeted improvement of endothelial cell function may offer new option for refractory ITP.…”