Can Immune Parameters Predict Acute and Chronic Rejection in Lung Recipients?
Condition: Lung Transplantation
Study type: Observational

Summary: 
      This study will evaluate the ability of lung transplant recipients to react to the
      transplanted organs. Previous research indicates that some immune tests can identify whether
      people are at risk for chronic rejection of transplanted lungs. Certain parameters, that is,
      physical properties involving the immune system, may cause acute chronic rejection of the
      lungs, which may lead to chronic rejection, a condition of scarring that worsens lung
      function. If such parameters can be identified and distinguished from those found in healthy
      subjects, information gained can help medical professionals to provide individualized
      treatments that work on the immune system. Short-term and long-term survival of lung
      transplant recipients may thus be improved.

      Patients who will have or have had lung transplants will be recruited by clinical transplant
      coordinators. Normal control subjects will be recruited through flyers and newspaper
      advertisements.

      Collection of blood samples will be done at Duke University Medical Center. Blood collections
      will be done of patients undergoing routine pretransplant and posttransplant blood tests, so
      no extra blood collections will be required. Control subjects will undergo three blood
      collections over an 8-week period. They will be compensated for their time in participating,
      at the rate of $5 for the initial blood draw, $10 for the second one, and $15 for the third
      one. A small amount of blood is involved, about 3 tablespoons. The blood cells and DNA (which
      contains genetic material) will be isolated for analysis. Patients' DNA samples collected
      will be identified by a code, and all other identifying information will be removed. The
      samples may be used in the future as new tests are developed.

      This study will not have a direct benefit for participants. However, during the study, if it
      is found that any patients have an inherited risk for a disease likely to cause early death
      if the disease is not treated, then the researchers will attempt to notify those patients.
      Overall, it is hoped that information gathered will enhance researchers' understanding of
      what tests best identify patients at risk for developing chronic rejection of their
      transplanted lungs.
    

Detailed description: 
      The aim of this study is to provide insight into the immune mechanisms involved in the pre-
      and posttransplant response of lung recipients to determine if short- and long-term graft
      outcome can be predicted and to allow for potential intervention. We have assembled a panel
      of assays that will test various functions of the immune response and investigate immune
      mechanisms involved in acute and chronic rejection (CR). Our overall hypothesis is that
      measurment of pre- and posttransplant immune response to donor HLA antigens/peptides can
      predict graft outcome. Our goal is to determine if immune parameters [ELISpot], intracellular
      T regulatory cells and ATP synthesis can identify lung recipients at high risk for developing
      AR and sub-clinical rejection. Sub-aim: To determine the correlation of cytokine genotypes
      with ELISpot results and T regulatory cell level and activity for recipients at high risk for
      developing acute rejection in comparison to a normal subject cohort. A second hypothesis is
      that recipients who experience an AR episode and remain responsive to donor antigen and those
      who show increased reactivity to donor HLA peptides are at high risk for developing CR. Our
      goal is to determine if the immune parameters (CFSE responder frequencies and response to
      donor peptides are assayed by CFSE, ELISpot, T regulatory cell level, and ATP synthesis) can
      identify lung recipients at high risk for developing CR and distinguish these immune
      parameters from a normal subject cohort. If successful, we will provide clinicians with the
      information necessary for individualization of immunosuppression intervention aimed at
      improving short and long-term graft outcome.
    

Keywords: Regulatory T Cells; Bronchiolitis Obliterans Syndrome; Genetic Polymorphism; Innate Immunity; Transplantation; Lung Transplantation