Elevated TCR-αβ+ double-negative T cells in pediatric patients with acquired aplastic anemia

Abstract

Background and aims: The pathophysiology of acquired aplastic anemia (aAA) is most associated with T cell mediated immune dysfunction, but the role of CD4^- CD8^- double negative T cells (DNTs) in pediatric patients with aAA is unclear. In this study, we aimed to investigate the proportion of TCR-αβ⁺ DNTs in pediatric patients with aAA and correlation with the response to immunosuppressive therapy (IST).

Materials and methods: Assessment of DNTs from peripheral blood was done by sensitive multi-color flow cytometry. The potential clinical value of TCR-αβ⁺ DNTs was then assessed by the receiver operating characteristic (ROC) curves.

Results: The retrospective study evaluated 164 pediatric patients with aAA and 105 healthy donors (HD). Our data showed higher proportion of TCR-αβ⁺ DNTs in total lymphocytes [1.04% (0.79%-1.40%) vs 0.69% (0.47%-0.87%), p < 0.001] and CD3⁺ T cells [1.52% (1.10%-1.96%) vs 1.10% (0.70%-1.40%), p < 0.001] in aAA compared to HD. Patients with SAA/VSAA achieving complete response (CR) after IST had a higher proportion of TCR-αβ⁺ DNTs at initial diagnosis, than those not achieving CR for total (1.21%±0.39 vs 0.78%±0.38, p < 0.05) and CD3⁺ T cells (1.74%±0.53 vs 1.15%±0.59, p < 0.05). The ROC analysis showed areas under the curves (AUCs) for TCR-αβ⁺ DNT proportion in lymphocytes and CD3⁺ T cells were 0.756 (cutoff value 1.33, p < 0.05) and 0.758 (cutoff value 1.38, p < 0.05), respectively. And the complete response rate was higher in TCR-αβ⁺ DNT proportion high group than in TCR-αβ⁺ DNT proportion low group at baseline (p < 0.001).

Conclusion: Our observations suggest that elevated TCR-αβ⁺ DNTs seems to play a role in the pathogenesis of aAA, and it was involve in immune response to IST.

Keywords: Aplastic anemia; Immunosuppressive therapy; Pediatric; double negative T cell.