title: Donor-derived soluble HLA plasma levels can not be used to monitor graft rejection in heart transplant recipients.
abstract: OBJECTIVE
  Increased levels of both donor- and recipient-derived HLA class I molecules (sHLA-I) can be found in serum or plasma of transplanted patients during rejection. Earlier data indicate that levels of donor-derived sHLA-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 expression in cardiac graft patients: donor-specific soluble antigen in a pre-sensitized graft patient. Transplant Proc 1991;23:2258-2260; Claas FHJ, Jankowska-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 an extended study with 34 heart transplant recipients, we used sHLA-I specific 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 plasma 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 the detection of sHLA molecules might explain this discrepancy. In order to test this hypothesis, patient sera were screened for the presence of anti-HLA 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 explain the low sHLA levels during rejection.
  
  
  CONCLUSIONS
  In heart transplantation increased donor-derived sHLA levels are not a suitable marker for rejection and that antibody formation can not explain these results. Therefore, monitoring rejection episodes on the basis of donor-derived soluble HLA molecules is not a realistic approach to decrease the number of biopsies after heart transplantation.
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Koelman
authors.forename: L M
authors.initials: LM
authors.lastname: Vaessen
authors.forename: A H
authors.initials: AH
authors.lastname: Balk
authors.forename: W
authors.initials: W
authors.lastname: Weimar
authors.forename: I I
authors.initials: II
authors.lastname: Doxiadis
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000818:Animals; D000917:Antibody Formation; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D015234:HLA-A Antigens / Q000097:blood* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000097:blood / Q000276:immunology; D015791:HLA-A3 Antigen / Q000097:blood / Q000276:immunology; D015235:HLA-B Antigens / Q000097:blood* / Q000276:immunology; D059949:HLA-B51 Antigen; D015793:HLA-B7 Antigen / Q000097:blood / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D051379:Mice; D012995:Solubility; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; C037709:HLA-A9 antigen; D015235:HLA-B Antigens; C035015:HLA-B12 antigen; D059949:HLA-B51 Antigen; D015793:HLA-B7 Antigen