Soluble donor HLA class I and beta(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 (2)m and total beta (2)m -free heavy chain (HC) in the serum of lung transplant recipients with ELIS A assays. While we were unable to detect specific donor beta (2)m-free HCs due to a lack of available antibodies, we could determine if events chat le d to an increase in the release of beta (2)m-free HC also led to an increas e in the release of donor sHLA/beta (2)m, particularly the 36 kDa, proteoly tically cleaved form. We found that lung transplants constituitively releas e donor sHLA/beta (2)m at ng/ml levels. The levels (bot-h of donor sHLA/bet a (2)m and total beta (2)m-free HIC) were significantly increased in CMV-se ro-negative recipients (but not in CMV-sero-positive recipients) at the ons et of post-transplant CMV disease. Acute rejection episodes were also assoc iated with an increased release of donor sHLA/beta (2)m, but not of beta (2 )m-free HC. However, in patients with particularly poor outcome (i.e., graf t loss within 1 year) there was a significant release of beta (2)m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of dono r-sHLA/beta (2)m. Our data are consistent with the hypothesis that the meta lloproteinase thar cleaves beta (2)m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and con trolled immune responses to donor may result in little or no activation of sHLA class I release, (C) American Society for Histocompatibility and Immun ogenetics, 2000. Published by Elsevier Science Inc.