Research identifies a predictor of chronic rejection after lung transplantation
Scientists have found that a protein called ZBTB7A may be an early predictor of graft rejection after lung transplantation. The study, described in the journal Science Translational Medicine, could open a way for the diagnosis and prevention of chronic lung allograft dysfunction.
Transplantation is a medical procedure in which an organ or tissue is transferred from one part of the body to another or from one individual to another. After decades of development, various organs have been successfully transplanted, such as heart, liver, lungs, kidneys, intestine, pancreas, and thymus. Lung transplantation, where a person's diseased lung is replaced by a deceased donor's healthy lung, is the last resort for advanced stage lung disease. Some examples of diseases that require a lung transplant are chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, and idiopathic pulmonary hypertension. However, the long-term outcomes of lung transplantation are somewhat disappointing: half of the patients die within 5 years after lung transplantation. One of the main factors that contribute to transplant failure is rejection, a process in which a recipient's immune system attacks the transplanted organ.
A team of scientists, headed by Dr. Thalachallour Mohanakumar at the Norton Thoracic Institute of St. Joseph's Hospital and Medical Center, has been studying the mechanisms of graft rejection following human lung transplantation over the past two decades. For the current study, Dr. Mohanakumar's team cooperated with scientists from Washington University School of Medicine and Aaron Diamond AIDS Research Center in order to better elucidate lung transplant rejection.
By working with mouse models and analyzing data from human patients, the researchers found that the expression of the protein ZBTB7A in alveolar macrophages might be an early predictor of chronic rejection. Patients who had higher ZBTB7A expression early on were more likely to be diagnosed with chronic rejection at last. Inhibition of ZBTB7A in alveolar macrophages alleviated airway disease and prevented chronic rejection of lung transplants in experimental animals.
Taken together, the findings suggest that monitoring the levels of ZBTB7A in alveolar macrophages may be a reliable method to predict chronic rejection after lung transplantation. This would facilitate the prevention and management of chronic lung allograft dysfunction.
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