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Keywords:

  • Clara cell protein;
  • Lysozyme;
  • MALDI-TOF;
  • MS;
  • Protein profile

Abstract

While lung transplant is an effective therapy for advanced lung disease, chronic allograph rejection remains a primary basis for lower survival rates than those for other solid organ transplants. This study used carefully controlled Zip-Tip extraction of bronchoalveolar lavage fluid (BALF) followed by MALDI-TOF MS to identify biomarkers of chronic lung transplant rejection. Many differences were observed between controls, those who did not develop chronic rejection within 100 months, and patients who had developed chronic rejection, diagnosed as bronchiolitis obliterans syndrome (BOS). Intensity ratios of peaks within the same MALDI-TOF profile were used to quantify the result. One of the best identifiers of BOS was a lowered ratio of clara cell protein (CCP m/z = 15 835) to lysozyme (m/z = 14 700), which gave 94% specificity and 74% sensitivity for diagnosis. Furthermore, low values for CCP/Lysozyme (<0.3) were observed in 66% of samples taken at 1 to 15 months prior to the diagnosis of BOS. Many other components of the profile gave similar or better outcomes for diagnosis but tended to be less valuable for the prediction of future disease. Overall, this study demonstrated the feasibility of this approach for the detection of disease biomarkers.