Donor-derived soluble HLA plasma levels can not be used to monitor graft rejection in heart transplant recipients

Objective: Increased levels of both donor- and recipient-derived HLA class I molecules (sHLA-I) can be found in serum or plasma of transplanted patien ts during rejection. Earlier data indicate that levels of donor-derived sHL A-I (dsHLA-I) correlate better with graft rejection than total sHLA Class I (Zavazava N, Kraatz E, Gassel AM, Muller-Ruchholtz W. Plasma MHC class I e xpression in cardiac graft patients: donor-specific soluble antigen in a pr e-sensitized graft patient. Transplant Proc 1991;23:2258-2260; Claas FHJ, J ankowska-Gan E, DeVito LD, et al, Monitoring of heart transplant rejection using a donor-specific soluble HLA class I ELISA. Hum Immunol 1993;37:121). Therefore, quantifying donor-derived soluble counterparts of HLA Class I ( sHLA-I) in the plasma of the recipient may offer a new possibility for non- invasive monitoring of rejection after organ transplantation. Methods: In a n extended study with 34 heart transplant recipients, we used sHLA-I specif ic ELISAs to monitor donor-derived soluble sHLA-A2, -A3, A9, -B7, -B12 and B51. Results: The assays were sensitive enough to detect dsHLA Class I in p lasma of the recipients. However, the levels of sHLA were not found to be a useful tool for monitoring rejection. Rejection was often associated with low levels of donor sHLA. The recent finding that antibodies can inhibit th e detection of sHLA molecules might explain this discrepancy. In order to t est this hypothesis, patient sera were screened for the presence of anti-HL A antibodies and the results were related to the donor-derived sHLA levels, Only in four out of 34 patients HLA Class I specific antibodies could expl ain the low sHLA levels during rejection. Conclusions: In heart transplanta tion increased donor-derived sHLA levels are not a suitable marker for reje ction and that antibody formation can not explain these results. Therefore, monitoring rejection episodes on the basis of donor-derived soluble HLA mo lecules is not a realistic approach to decrease the number of biopsies afte r heart transplantation. (C) 2000 Elsevier Science B.V. All rights reserved .