Soluble donor HLA class I and beta sub(2)m-free heavy chain in serum of lung transplant recipients: steady-state levels and increases in patients with recurrent CMV infection, acute rejection episodes, and poor outcome

We determined the concentration of donor sHLA/ beta sub(2)m and total beta sub(2)m-free heavy chain (HC) in the serum of lung transplant recipients with ELISA assays. While we were unable to detect specific donor beta sub(2)m-free HCs due to a lack of available antibodies, we could determine if events that led to an increase in the release of beta sub(2)m-free HC also led to an increase in the release of donor sHLA/ beta sub(2)m, particularly the 36 kDa, proteolytically cleaved form. We found that lung transplants constitutively release donor sHLA/ beta sub(2)m at ng/ml levels. The levels (both of donor sHLA/ beta sub(2)m and total beta sub(2)m-free HC) were significantly increased in CMV-sero-negative recipients (but not in CMV-sero-positive recipients) at the onset of post-transplant CMV disease. Acute rejection episodes were also associated with an increased release of donor sHLA/ beta sub(2)m, but not of beta sub(2)m-free HC. However, in patients with particularly poor outcome (i.e., graft loss within 1 year) there was a significant release of beta sub(2)m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of donor-sHLA/ beta sub(2)m. Our data are consistent with the hypothesis that the metalloproteinase that cleaves beta sub(2)m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and controlled immune responses to donor may result in little or no activation of sHLA class I release.