G. Devouassoux et al., Early lung leukocyte infiltration, HLA and adhesion molecule expression predict chronic rejection, TRANSPL IMM, 8(4), 2001, pp. 229-236
Obliterative bronchiolitis remains the main cause of graft dysfunction and
death after 1 year. Defined by an irreversible airway obstruction, bronchio
litis obliterans syndrome is usually recognized in the advanced stage of th
e disease, with histological evidence of fibrotic damage. Fibrosis represen
ts the end-stage of an inflammatory process, leading to the postulate that
chronic lung graft dysfunction is preceded by cellular and molecular events
. This study was performed during the first year following lung transplanta
tion, in the absence of histological or functional criteria of chronic reje
ction. Transbronchial biopsies from eight lung allografts were examined. Fo
ur developed a bronchiolitis obliterans syndrome (Group I), and 1 had good
outcomes (Group II) at 2 years, Using immunohistochemistry, the aim of the
study was to correlate early immunological events with graft outcomes at 2
years. An up-regulation of HLA class I antigen (P = 0.0001), an overexpress
ion of Ki=67 (P = 0.006) on bronchial epithelium, and graft infiltration by
CD45 +, CD25 + cells (P = 0.003) were significantly associated with the de
velopment of chronic rejection. An overexpression of numerous adhesion mole
cules was observed. However, only very late antigen-4 had a discriminative
value (P = 0.04), preceding chronic graft dysfunction. Our results suggest
that graft dysfunction is associated with early molecular and cellular even
ts, and raises the possibility that a fibroproliferative disorder is initia
ted shortly after transplantation. The recognition of such early immunologi
cal markers might facilitate improved graft management and prognosis. (C) 2
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