Work

Zinc Status Affects T Cell Reconstitution after Transplant in Patients Receiving Naïve-T Cell Depleted Allo-Transplants

Year: 2024

Type: article

Abstract: Immune reconstitution (IR) of the T cell compartment is a major contributor to post-allogeneic hematopoietic stem cell transplant (allo-HSCT) outcomes. The thymus is the organ naturally generating the T cells and ensures central tolerance; however, HSCT itself, GVHD, corticosteroids, age and several unknown factors cause thymic damage and limit its capacity of regeneration. Zinc (Zn) is a crucial microelement for the normal function of the immune system; zinc deficiency (ZD) causes T cell lymphopenia and depressed thymic function. The prevalence and the effect of ZD among allo-HSCT recipients is unknown. We hypothesized that peri-HSCT ZD affects T cell IR. We analyzed serum Zn levels of allo-HSCT patients who received naïve T cell (TN) depleted grafts as a strategy to prevent aGVHD. This population is very interesting because, in these patients, circulating TN at d+365 after HSCT will be of donor hematopoietic stem cell origin generated in the recipient thymus. Samples and clinical data were prospectively collected. Fifty-two patients had serum samples available for Zn measures, as pre-HSCT and/or day +80 samples. Zn measures were performed through mass spectrometry. ZD was defined for Zn<70ug/dL. T cell populations were analyzed by flow cytometry at day+365. PBMC pellets collected at d+365 were analyzed for the expression of signal-joint T cell receptor excision circles (sjTRECs), the gold standard for measuring thymic-derived T cells. We studied the association between Zn levels at baseline and day+80 and parameters of IR through linear regression. Comparisons between two groups were analyzed by t-test. Patients’ characteristics are outlined in the table. Forty-one patients (78.8%) had pre-HSCT and 46 (88.5%) had day+80 Zn measures; 38 patients (73.1%) had both pre-HSCT and day+80 Zn measures. At baseline, 13 patients (25%) had ZD, whereas seven (13.3%) were ZD at day+80. Median sjTRECs at day +365 were 3.33/mg of DNA (range 0.00-16,704.54). As expected, sjTRECs at day+365 significantly correlated with age at transplant (r2=0,3824; p<0.0001), whereas Zn levels pre-HSCT or day+80 did not. The number of circulating CD4+ and CD8+ TN at day+365 showed significant correlation with age. Zinc levels did not correlate with IR of absolute CD4+, CD8+, NK, T regs, and B cells at day+365. However, day+80 serum Zn was significantly associated with sjTRECs (Figure 1A. r2=0.2643; p=0.0019) and lower pre-HSCT Zn significantly correlated with worse CD8+TN reconstitution at day+365 (Figure 1B. r2=0.1433; p= 0.0327), with clear trends in the same direction also for pre-HSCT Zn and CD4+ TN and day+80 Zn and CD4+ TN at day 365. In conclusion, a non-negligible population of patients undergo allo-HSCT with unrecognized ZD that can negatively affect IR on the thymic-derived T cell compartment. Early recognition of ZD and zinc supplementation might help prevent morbidity related to poor IR in a proportion of patients.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.427