The short-term predictive value of CD4+ cells for combination therapy with high-dose dexamethasone and immunoglobulin in newly diagnosed primary immune thrombocytopenia patients

Abstract

Introduction: Dexamethasone (DXM) or immunoglobulin (IVIg) are first-line therapies for primary immune thrombocytopenia (ITP), with an effective rate of 80 %. Some patients with both severe bleeding symptoms and platelet counts of <30 × 10⁹/L received a combination of DXM and IVIg. Autoimmune disorders, especially involving CD4⁺ T-cells, play a key role in the pathogenesis of ITP. We assumed that variations in the immune status of CD4⁺ T-cells will lead to different treatment responses. Until now, there have been few relevant clinical studies on CD4⁺ T-cells and the outcome of first-line therapies.

Methods: A prospective study enrolling 42 newly diagnosed ITP patients and 30 normal control volunteers was performed. The profiles of major CD4⁺ T-cells, including T helper (Th)1, Th2, Th17, and regulatory T (Treg) cells, and the related levels of interleukin (IL)-2, IL-17, and IL-23 were examined. The platelet number was recorded at the time point of day 0, day 14, and day 30.

Results: Greater concentrations of Th1 and Th17 cells and lower relative numbers of Treg cells were found in the ITP group. As for the treatment outcome on day 14, the profiles of Th2 and IL-2 were significantly greater in the NR group, while the expression of IL-17 was elevated in the CR group. As for the treatment outcome on day 30, higher levels of Th2 cells were observed in those patients who needed 2× pulses of HD DXM compared to those who needed only 1× pulse of HD DXM and IVIg, and receiver operating characteristic curve analysis showed that lower Treg cell may predict favorable values. Meanwhile, the higher IL-23 value may predict a poor early response.

Conclusions: Our results indicate that Th1, Th17, and Treg cells and IL-2 and IL-23 participate in the onset of ITP. Higher profiles of Th2, IL-2 and IL-23 may predict poor treatment outcomes. Higher levels of IL-17 and lower profile of Treg may predict sensitivity to HD DXM and IVIg combination therapy.

Keywords: CD4(+) T cells; Dexamethasone; Immunoglobulin; Interleukin-17; Interleukin-2; Interleukin-23; Primary immune thrombocytopenia.