According to the American Transplant Foundation, more than 113,000 people in the U.S. alone are on waiting lists for an organ. There are about 18 deaths every day as a result of organ unavailability.1 With donor organs so scarce, it is of the utmost importance that the people who are fortunate enough to be recipients are given the best chance of recovery.
Proteomics now presents an opportunity to find noninvasive tools for monitoring patients after transplant and, where possible, identifying a biomarker for allograft rejection and chronic dysfunction.
A lung transplant is the only option for many end-stage lung diseases, such as cystic fibrosis or chronic obstructive pulmonary disease. The most common cause of long-term death in these patients is chronic rejection, manifesting as bronchiolitis obliterans syndrome (BOS) where scarring occurs in the patient’s airways, obstructing airflow. BOS is diagnosed by periodic spirometric evaluation. A decrease in forced expiratory volume per second, or FEV1, is indicative of obstruction. Unfortunately, there are a number of factors associated with BOS that impact survival.2 More accurate diagnostics are needed to initiate early intervention and prevent rejection and death.
Kosanam et al.3 have developed a new protocol to find biomarkers of allograft rejection. Biomarkers of organ rejection could significantly aid transplant patients by providing a means of identifying chronic graft dysfunction early.
Kosanam et al.3 used bronchoalveolar lavage fluid to obtain samples from transplant patients with symptoms of chronic graft dysfunction and those who were asymptomatic. An LTQ-Orbitrap XL Mass Spectrometer (Thermo Scientific) was used to conduct a differential proteomic analysis of the bronchoalveolar lavage fluid. This particular study produced results that were not consistent with all the previously defined biomarkers for chronic graft dysfunction. By the same token, additional biomarkers for long-term rejection were identified. The fractionation methods used by Kosanam et al. were at least partly responsible for the differing outcomes between this particular study and others. Previous studies did not employ fractionation to their methodology. These, in combination with nanospray ionization/high resolution Orbitrap mass spectrometry (Thermo Scientific), have led to the detection of 531 proteins, one of the largest datasets of bronchoalveolar lavage fluid proteins in lung transplant patients to date. Additionally, investigators compared the bronchoalveolar lavage fluid proteome with serum proteins to ensure that none of those detected were serum proteins that had leaked into alveolar space during posttransplant reperfusion.
This newly described protocol provides a method for enhancing the sensitivity of tests to detect proteins that are less abundant in bronchoalveolar lavage fluid. While the sample size was small, investigators were able to draw out sufficient evidence to move to larger cohort studies to validate their findings. Arming ourselves with a biomarker for long-term rejection could have potential life-saving outcomes for over 30,000 recipients of lung transplants in the U.S each year. Perhaps we could go even further to say that the ability to draw out a biomarker for chronic graft dysfunction after a lung transplant could be applied to finding a biomarker for the same in the 100,000 organ transplants in the U.S. every year.4 With there already being a global shortage of organs available for transplant, the ability to mediate complications and preserve transplanted organs would certainly be welcomed.
1. American Transplant Foundation, http://www.americantransplantfoundation.org/about-transplant/facts-and-myths/
2. Parada, M.T., Alba, A., and Sepulveda, C. (2010) ‘Bronchiolitis obliterans syndrome development in lung transplantation patients‘, Transplantation Proceedings, 42 (1), (pp. 331-332)
3. Kosanam, H., et al. (2012) ‘Differential proteomic analysis of bronchoalveolar lavage fluid from lung transplant patients with and without chronic graft dysfunction‘, Clinical Biochemistry, 45 (3), (pp. 223-230)
4. Bentley, T.S., Hanson, S.G., and Hauboldt, R.H. (2011) ‘2011 U.S Organ and tissue transplant costs estimates and discussion‘, Millman Research Report.
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