Effect of Immunosuppression on Target Blood Immune Cells Within 1 Year After Lung Transplantation: Influence of Age on T Lymphocytes

Abstract

BACKGROUND Lymphocytes are targeted by immunosuppressive therapy in solid organ transplantation and they influence allograft outcome. MATERIAL AND METHODS Peripheral blood lymphocyte subsets (PBLS) determined by flow cytometry during the first year post-transplant from patients who underwent a first lung transplantation in a French University Hospital between December 2011 and July 2013 were retrospectively analyzed according to recipient characteristics and allograft outcome. RESULTS Fifty-seven recipients were enrolled and 890 PBLS were collected. T lymphocytes and NK cells were rapidly decreased, below normal range, from the first postoperative days. B cells decreased more gradually, remaining within normal range, with the lowest level reached after day 100. In multivariate analysis, greater T lymphopenia was found in older recipients (-414 [-709 to -119] cells/µL, p=0.007). According to the outcome, multivariate analysis evidenced lower levels of lymphocytes when bacterial and viral infection occurred (-177 [-310 to -44] cells/µL, p=0.009 and (-601 [-984 to -218] cells/µL, p=0.002, respectively), higher CD8+ T lymphocytes with BOS (+324 [+94 to +553] cells/µL, p=0.006), and higher leukocytes with restrictive allograft syndrome (+3770 [+418 to +7122] cells/µL, p=0.028). CONCLUSIONS Aging is associated in our cohort with more severe T lymphopenia after induction therapy for lung transplantation. The analysis of leukocytes and PBLS is associated with specific profile according to the allograft outcome.

Figure 1

Kinetics of peripheral blood lymphocyte subsets (PBLS) over the first year post-transplantation. Y-axis=cell counts in cells/μL and X-axis=time post-transplant in days. Curves represent the smoothed mean with confidence interval. Values before zero represent the pooled counts realized within 3 months before LTx. Red color represents area below inferior normal thresholds from healthy controls.

Figure 2

T lymphocytes according to the age. (A) Scatterplot and fitted linear regression (blue line) with confidence interval (grey fill). Pearson correlation test, r=coefficient of correlation. (B) Kinetics of T lymphocytes over the first year post-transplantation according to age in decades. Y-axis= cell counts in cell/μL and X-axis=time post-transplant in days. Curves represent the smoothed mean with confidence interval. Values before zero represent the pooled counts realized within 3 months before LTx. Red line represents the inferior normal threshold from healthy controls.

Figure 3

Kinetics of peripheral blood lymphocyte subsets (PBLS) over the first year post-transplantation according to age groups (median). Y-axis=cell counts in cells/μL and X-axis=time post-transplant in days. Grey curves=recipients ≤ median age (48 years old). Black curves= recipients > median age. Curves represent the smoothed mean with confidence interval. Values before zero represent the pooled counts performed within 3 months before LTx. Red color represents the area below inferior normal thresholds from healthy controls. Analysis by linear mixed model: beta estimation of cell counts differences with confidence interval and p value.

Figure 4

ROC curves of CD4+ T cell counts realized within the first year for diagnosis of infection (bacterial and viral). AUC: area under the curve.