Activated CD4 + T lymphocyte is a potential biomarker for acute graft-vs.-host disease after hematopoietic stem cell transplantation in children with transfusion-dependent β-thalassemia

Abstract

BackgroundAcute graft-vs.-host disease (aGVHD) is still one of the most common and life-threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT). Whether or not the level of activated T lymphocytes rises before the onset of aGVHD is unknown. We explored the possibility of T lymphocytes as biomarkers for early prediction of aGVHD in children with transfusion-dependent β-thalassemia (TDTβ).MethodsWe retrospectively analyzed the characteristics of T lymphocyte subsets before and 14 days after HSCT in children with TDTβ who developed aGVHD. Data from 95 children (Age ≤ 14 years) who underwent allogeneic HSCT from January 2020 to December 2021 were collected. Patients were divided into non-aGVHD group (n = 55) and aGVHD group (n = 40), and aGVHD group was divided into two subgroups: grade I aGVHD (n = 16) and grade II-IV aGVHD (n = 24). Receiver operating characteristic curve (ROC) analysis was performed to predict aGVHD.ResultsBefore preconditioning in non-aGVHD and aGVHD groups, there was no significant difference in all lymphocyte subsets and ratio of CD4 + /CD8 + T cells. On day 14 post-transplantation in non-aGVHD and aGVHD groups, the absolute concentrations per μl blood of T cells, CD4 + T cells, CD8 + T cells, activated CD4 + T cell and NK cells, were 69.73 (14.70, 137.77) and 140.36 (65.06, 293.42), 10.00 (2.35, 23.59) and 35.91 (12.41, 68.71), 37.25 (5.82, 84.36) and 89.99 (35.83, 180.81), 0.52 (0.17, 2.20) and 4.08 (0.91, 11.12), 43.86 (15.00, 91.31) and 26.35 (15.19, 49.39), respectively. On day + 14 (14 days post-transplantation), the differences in all cell subsets and the ratio of CD4 + /CD8 + T cells were not statistically significant between grade I aGVHD and grade II-IV aGVHD subgroups. The absolute concentrations of CD8 + T cells in grade I aGVHD were significantly higher than in grade II-IV aGVHD [128.21 (61.11, 258.91) vs. 60.81 (21.59, 176.38), P = 0.057]. AUC of NK cells, CD8 + T cells, T cells, CD4 + T cells, and CD4 + CD25 + T cells were 0.6275, 0.6839, 0.7068, 0.7241, and 0.7589, and cut-off values were 73.75 (97.50, 34.55), 146.90 (37.50, 94.55), 187.30 (45.00, 90.91), 18.95 (70.00, 72.73), and 3.24 (52.50, 87.27), respectively. The AUC of the combined CD4 + CD25 + T cells and CD8 + T cells, CD4 + CD25 + T cells and T cells, CD4 + CD25 + T cells and CD4 + T cells, CD4 + CD25 + T cells and NK cells, respectively, were 0.7500, 0.7598, 0.7750, and 0.8050.ConclusionOur findings demonstrate that level of activated CD4 + T cells on day + 14 (post-HSCT) is a valuable biomarker for predicting aGVHD in children with TDTβ and CD8 + T cells could likely be a biomarker for severe aGVHD.

Forming a new perspective: Post‐structural approaches to determination of donor compatibility and post‐transplant assessment of allograft health

“…The post‐transplant phenotypical characterisation of lymphocyte subsets as a means of assessing the functional status of the recipient immune system presents an appealing prospect for the routine diagnostic laboratory. Reports of the association of transitional B cell subsets and long‐term outcomes of renal transplantation (Sharma 2017), higher CD4+ counts associated with higher risk of allograft rejection (Abdullah et al 2022), of activated CD4+ T cells as predictors of a GvHD in children (Huang et al 2022), of changes in B cell profile linked to poor vaccine response (Schuller et al 2022) and of antibody‐mediated renal allograft rejection correlated with increased CD28‐CD8+ T cells (Mai et al 2022) represent a selection of more recent papers on this topic. However, consensus has yet to emerge in regard to the diagnostic value of such tests and no literature currently exists which uses lymphocyte phenotyping to prospectively direct post‐transplant patient management.…”