Table 2.
VZV-specific immune responses of allogeneic hematopoietic stem cell transplantation recipients.
| VZV non-responders | VZV responders | P | ||
|---|---|---|---|---|
| (n = 42)* | (n = 15) | |||
| 7-day VZV-stimulated PBMC, median [IQR] | ||||
| IFN-γ release (pg/mL) | 0.22 [0.12–0.42] | 80.45 [54.3–312.8] | <.0001 | |
| EdU+ proliferating cells among CD3+ cells (%) | 0.002 [0.001–0.11] | 2.22 [1.18–7.56] | <.0001 | |
|
24-h VZV-stimulated whole blood
†, median [IQR] |
||||
| ifn-γ gene expression (fold change) | 0.85 [0.55–1.44] | 12.99 [5.30–79.79] | <.0001 | |
| Immunophenotyping of lymphocytes and subsets (cells/µL), median [IQR] | ||||
| ALC | 1,090 [710–2,460] | 1,590 [1,000–2,130] | .421 | |
| T CD4+ | 232.5 [115.5–385.5] | 287 [220.5–329] | .319 | |
| T CD4+ N | 12.5 [4.75–22.25] | 33 [14.5–38] | .043 | |
| T CD4+ CM | 40 [17–80] | 81 [65.5–114] | .010 | |
| T CD4+ EM | 115 [80–208] | 157 [116.5–192.5] | .459 | |
| T CD4+ DM | 5.5 [1.75–38.75] | 3.5 [0–5.75] | .106 | |
| T CD8+ | 367.5 [218.75–879.25] | 364 [237.5–486] | .921 | |
| T CD8+ N | 16.5 [9–50.5] | 44 [24–70.5] | .048 | |
| T CD8+ CM | 10 [2–14.5] | 16 [7–30] | .125 | |
| T CD8+ EM | 160 [69.5–282.75] | 157 [108.5–303] | .490 | |
| T CD8+ DM | 225 [60–332] | 102 [64.5–140] | .287 | |
| NK cells | 157 [114–137] | 146 [99.5–194] | 0.39 | |
| Post-transplant VZV IgG titers at inclusion (mIU/mL), median [IQR] | 383.1 [141.1–664.2] | 1382 [494.4–1577] | .005 | |
| Selected clinical variables, n (%) | ||||
| AML | 20 (48) | 9 (60) | .715 | |
| ATG | 24 (57) | 9 (60) | >.999 | |
| DLI | 5 (12) | 3 (20) | .422 | |
| Chronic GvHD | 5 (12) | 3 (20) | .422 | |
| IS therapy‡ | 15 (36) | 4 (27) | .751 | |
Peripheral blood mononuclear cells (PBMC) (1 × 105 cells) and whole blood from allo-HSCT recipients (n = 57) were stimulated by VZV antigen (inactivated supernatants from VZV-infected MRC-5 cells, 20 µg/ml) or supernatants from VZV-uninfected MRC-5 cells (control condition). IFN-γ release (pg/ml) and the percentage of EdU+ proliferating cells (among CD3+ cells) were measured after a 7-day VZV stimulation of PBMC by immunoassay (ELLA nanofluidic system) or flow cytometry, respectively. VZV responders were identified based on IFN-γ release strictly above 4.83 pg/ml, corresponding to twice the maximum value observed in the control condition. The ifn-γ gene expression level was measured by qPCR in a whole blood sample after 24 h of VZV stimulation. The relative differential expression between VZV-stimulated and non-stimulated conditions is given as the fold change. Immunophenotyping of lymphocyte subsets was performed by flow cytometry on whole blood. Groups were compared using the Mann–Whitney U test or the Fisher’s exact test, where appropriate; P-values <.05 were considered statistically significant and are highlighted in bold. *Data were missing for three allo-HSCT recipients. †Data were missing for three allo-HSCT recipients. ‡Immunosuppressive therapy: cyclosporine, tacrolimus, corticosteroids, ruxolitinib. Abbreviations: ALC, absolute lymphocyte count; AML, acute myeloid leukemia; ATG, antithymocyte globulin; CM, central memory; DM, differentiated memory; DLI, donor lymphocyte infusion; EdU, 5-ethynyl-2′-deoxyuridine; EM, effector memory; GvHD, graft-versus-host disease; IFN-γ, interferon-γ; IgG, immunoglobulin G; IQR, interquartile range; IS, immunosuppressive; N, naïve; VZV, varicella zoster virus.