TY - JOUR

T1 - The number of FoxP3+ cells in transbronchial lung allograft biopsies does not predict bronchiolitis obliterans syndrome within the first five years after transplantation

AU - Krustrup, Dorrit

AU - Iversen, Martin

AU - Martinussen, Torben

AU - Schultz, Hans Henrik L

AU - Andersen, Claus B.

PY - 2015/3

Y1 - 2015/3

N2 - Background: An important limitation to the success of lung transplantation is the development of bronchiolitis obliterans syndrome (BOS). It has been hypothesized that regulatory T lymphocytes (Tregs) are related to the risk of BOS. We aim to evaluate whether the number of forkhead box P3 (FoxP3+) cells/mm2 in lung allograft biopsies is a predictor of long-term outcome. Materials and Methods: A total of 58 consecutive lung transplant patients were included in the study. For 233 routine surveillance biopsy samples, the numbers of FoxP3+ cells/mm2 were assessed by immunohistochemical staining with antibodies against FoxP3. BOS scores were calculated for the first five yr after transplantation. Results: We determined that acute rejection was related to the time elapsed from transplantation to BOS with hazard ratios of 3.18 (p = 0.02) and 3.73 (p = 0.04) when comparing the levels of acute rejection grade 1 and grade 2/3, respectively, to no rejection. According to a Cox regression analysis, the number of FoxP3+ cells/mm2 was not predictive of time to BOS. Discussion and Conclusions: Our data indicate that the number of FoxP3+ cells in the lung allograft did not correlate with BOS-free survival time. Previous studies have been contradictory and included different time points. Our findings emphasize the importance of including a time factor.

AB - Background: An important limitation to the success of lung transplantation is the development of bronchiolitis obliterans syndrome (BOS). It has been hypothesized that regulatory T lymphocytes (Tregs) are related to the risk of BOS. We aim to evaluate whether the number of forkhead box P3 (FoxP3+) cells/mm2 in lung allograft biopsies is a predictor of long-term outcome. Materials and Methods: A total of 58 consecutive lung transplant patients were included in the study. For 233 routine surveillance biopsy samples, the numbers of FoxP3+ cells/mm2 were assessed by immunohistochemical staining with antibodies against FoxP3. BOS scores were calculated for the first five yr after transplantation. Results: We determined that acute rejection was related to the time elapsed from transplantation to BOS with hazard ratios of 3.18 (p = 0.02) and 3.73 (p = 0.04) when comparing the levels of acute rejection grade 1 and grade 2/3, respectively, to no rejection. According to a Cox regression analysis, the number of FoxP3+ cells/mm2 was not predictive of time to BOS. Discussion and Conclusions: Our data indicate that the number of FoxP3+ cells in the lung allograft did not correlate with BOS-free survival time. Previous studies have been contradictory and included different time points. Our findings emphasize the importance of including a time factor.

KW - Acute rejection

KW - Bronchiolitis obliterans syndrome

KW - Forkhead box P3

KW - Histopathology

KW - Lung transplantation

KW - Regulatory T cells

UR - http://www.scopus.com/inward/record.url?scp=84925235581&partnerID=8YFLogxK

U2 - 10.1111/ctr.12502

DO - 10.1111/ctr.12502

M3 - Journal article

C2 - 25533723

AN - SCOPUS:84925235581

VL - 29

SP - 179

EP - 184

JO - Clinical Transplantation

JF - Clinical Transplantation

SN - 0902-0063

IS - 3

ER -