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Clinical Trial
. 2012 Nov;14(10):1258-75.
doi: 10.3109/14653249.2012.715243. Epub 2012 Sep 18.

Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation

Affiliations
Clinical Trial

Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation

VSports最新版本 - Mark Bosch et al. Cytotherapy. 2012 Nov.

Abstract

Background aims: Anti-thymocyte globulin (ATG) is being used increasingly to prevent graft-versus-host disease (GvHD); however, its impact on immune reconstitution is relatively unknown. We (i) studied immune reconstitution after ATG-conditioned hematopoietic cell transplantation (HCT), (ii) determined the factors influencing the reconstitution, and (iii) compared it with non-ATG-conditioned HCT VSports手机版. .

Methods: Immune cell subset counts were determined at 1-24 months post-transplant in 125 HCT recipients who received ATG during conditioning V体育安卓版. Subset counts were also determined in 46 non-ATG-conditioned patients (similarly treated). .

Results: (i) Reconstitution after ATG-conditioned HCT was fast for innate immune cells, intermediate for B cells and CD8 T cells, and very slow for CD4 T cells and invariant natural killer T (iNKT) (iNKT) cells V体育ios版. (ii) Faster reconstitution after ATG-conditioned HCT was associated with a higher number of cells of the same subset transferred with the graft in the case of memory B cells, naive CD4 T cells, naive CD8 T cells, iNKT cells and myeloid dendritic cells; lower recipient age in the case of naive CD4 T cells and naive CD8 T cells; cytomegalovirus recipient seropositivity in the case of memory/effector T cells; an absence of GvHD in the case of naive B cells; lower ATG serum levels in the case of most T-cell subsets, including iNKT cells; and higher ATG levels in the case of NK cells and B cells. (iii) Compared with non-ATG-conditioned HCT, reconstitution after ATG-conditioned HCT was slower for CD4 T cells, and faster for NK cells and B cells. .

Conclusions: ATG worsens the reconstitution of CD4 T cells but improves the reconstitution of NK and B cells VSports最新版本. .

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"VSports app下载" Conflict of interest statement

Disclosure of Interest: J. S. has received a grant from Genzyme, Otherwise the authors declare no competing financial interests V体育平台登录.

Figures

Figure 1
Figure 1. Median immune cell subset counts in recipients of ATG-conditioned blood stem cell transplantation
The time points displayed are before transplantation (pre-conditioning) and day 7, 28, 56, 84, 180, 365 and 730 after transplantation (for Ig levels, days 7 and 56 were unavailable). Error bars indicate the 25th to 75th percentiles. Stars indicate a significant difference (P < .05) from graft donors. Normal values (derived from graft donors) are shown as horizontal lines (solid black lines for the 10th and 90th percentiles and dotted line for the median). Days after transplantation are shown on all x-axes. On all y-axes, values are cells per microliter blood, except for neutrophils (per nanoliter blood) and IgM, IgG, and IgA (g/L serum).
Figure 1
Figure 1. Median immune cell subset counts in recipients of ATG-conditioned blood stem cell transplantation
The time points displayed are before transplantation (pre-conditioning) and day 7, 28, 56, 84, 180, 365 and 730 after transplantation (for Ig levels, days 7 and 56 were unavailable). Error bars indicate the 25th to 75th percentiles. Stars indicate a significant difference (P < .05) from graft donors. Normal values (derived from graft donors) are shown as horizontal lines (solid black lines for the 10th and 90th percentiles and dotted line for the median). Days after transplantation are shown on all x-axes. On all y-axes, values are cells per microliter blood, except for neutrophils (per nanoliter blood) and IgM, IgG, and IgA (g/L serum).
Figure 1
Figure 1. Median immune cell subset counts in recipients of ATG-conditioned blood stem cell transplantation
The time points displayed are before transplantation (pre-conditioning) and day 7, 28, 56, 84, 180, 365 and 730 after transplantation (for Ig levels, days 7 and 56 were unavailable). Error bars indicate the 25th to 75th percentiles. Stars indicate a significant difference (P < .05) from graft donors. Normal values (derived from graft donors) are shown as horizontal lines (solid black lines for the 10th and 90th percentiles and dotted line for the median). Days after transplantation are shown on all x-axes. On all y-axes, values are cells per microliter blood, except for neutrophils (per nanoliter blood) and IgM, IgG, and IgA (g/L serum).
Figure 2
Figure 2. Effects of naïve CD4 T cell graft content (top) and of recipient age (bottom) on naïve CD4 T cell counts on day 28, 56, 84, 180 and 365 post transplant
Correlation trend line is shown in case of p<0.05. On x-axes, the naïve CD4 T cell number in graft is expressed as ×106/kg recipient body weight, and the recipient age at the time of transplantation is expressed as years. On all y-axes, naïve CD4 T cell counts are per microliter blood.
Figure 3
Figure 3. Effect of recipient CMV serostatus (pretransplant) on memory/effector CD8 T cell counts
Shown are total memory/effector CD8 T cells, CD45RAnegative (memory-like) memory/effector CD8 T cells, and CD45RApositive (terminally differentiated) memory/effector CD8 T cells. Asterisks (*) denote p<0.05 (Man-Whitney rank sum test). On all y-axes, displayed are cell counts per microliter blood.
Figure 4
Figure 4. Effect of GVHD on naive B cell counts
ATG-conditioned and non- ATG-conditioned patients were divided into those with vs. without significant GVHD (grade 2–4 aGVHD or cGVHD requiring systemic immunosuppressive therapy at any time during follow up). Asterisk (*) denotes p<0.05 per the Mann-Whitney rank sum test. On y-axis, displayed are naïve B cell counts per microliter blood.
Figure 5
Figure 5. Effect of day 7 ATG serum levels on day 28, 56, 84, 180 and 365 counts of naïve (top) and memory/effector (bottom) CD8 T cells
Trend line is shown in cases of p<0.05 as determined by Spearman rank correlation, demonstrating that higher day 7 ATG levels were associated with lower cell counts. On all x-axes, displayed are ATG levels on day 7 as mg/L serum. On all y-axes, displayed are cell counts per microliter blood.
Figure 6
Figure 6. Median immune cell subset counts in recipients of blood stem cells from HLA-matched siblings conditioned with ATG (black diamonds) vs. without ATG (gray squares)
The time points displayed are 1, 3, 6 and 12 months after transplantation. Error bars indicate the 25th to 75th percentiles. Stars indicate a significant difference (P < .05) between ATG-conditioned and non-ATG-conditioned patients. Normal values are shown as horizontal dashed lines (10th and 90th percentiles). Days after transplantation are shown on all x-axes. On all y-axes, values are cells per microliter blood.

References

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