Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens.
BACKGROUND
Rejection and obliterative bronchiolitis are barriers to sustained graft function in recipients of transplanted lungs. Early detection is hindered by inadequate tests and an incomplete understanding of the molecular events preceding or accompanying graft deterioration.


METHODS
Hypothesizing that genes involved in immune responses and tissue remodeling produce biomarkers of rejection, we measured the expression of 192 selected genes in 72 sets of biopsy specimens from human lung allografts. Gene transcripts were quantified using a 2-step, multiplex, real-time polymerase chain reaction approach in endobronchial and transbronchial biopsy specimens from transplant recipients without acute infections undergoing routine surveillance bronchoscopy.


RESULTS
Comparisons of histopathology in parallel biopsy specimens identified 6 genes correlating with rejection as manifested by lymphocytic bronchitis, a suspected harbinger of obliterative bronchiolitis. For example, beta2-defensin and collagenase transcripts in inflamed bronchi increased 37-fold and 163-fold, respectively. By contrast, these transcripts did not correlate with acute rejection in transbronchial specimens. Further, no correspondence was noted between histopathologic bronchitis and parenchymal rejection when endobronchial and transbronchial samples were obtained from the same patient.


CONCLUSIONS
Our highly sensitive method permits quantitation of many gene transcripts simultaneously in small, bronchoscopically acquired biopsy specimens of allografts. Transcript signatures obtained by this approach suggest that airway and alveolar responses to rejection differ and that endobronchial biopsy specimens assess lymphocytic bronchitis and chronic rejection but are not proxies for transbronchial biopsy specimens. Further, they reveal changes in airway expression of the specific genes involved in host defense and remodeling and suggest that the measurement of transcripts correlating with lymphocytic bronchitis may be diagnostic adjuncts to histopathology.
Xu
Xiang
X
Department of Medicine University of California at San Francisco, San Francisco, 94143, USA.
Golden
Jeffrey A
JA
Dolganov
Gregory
G
Jones
Kirk D
KD
Donnelly
Samantha
S
Weaver
Timothy
T
Caughey
George H
GH
D000328:Adult; D001707:Biopsy, Needle; D001989:Bronchiolitis Obliterans / Q000473:pathology*; D001999:Bronchoscopy; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D006084:Graft Rejection / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects* / Q000379:methods; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020871:RNA Stability / Q000235:genetics*; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous
D005819:Genetic Markers