IMMUNE REACTIVITY TOWARDS HLA CLASS II DETERMINANTS DURING THE FIRST YEAR POST RENAL TRANSPLANTATION.
A Iniotaki-Theodoraki, P Douramani, J Boletis, A Papassavas, G Trigas, A Kostakis and C Stavropoulos-Giokas, Department of Immunology and National Tissue Typing Center, General Hospital, Athens, Greece.
Missmatch (mm) at HLA-DR molecules has a strong detrimental effect on graft survival. In this study, the frequency of activated T cells recognizing donor HLA-DR allopeptides and the appearance of HLA-class II donor specific antibodies were evaluated in renal transplant recipients during the first year post-Tx. Sequential samples of blood were collected from 30 renal transplant recipients starting 10 days post transplantation and continued over a period of 12 months. All patients had received graft from one haplotype matched living donors (sharing one DR antigen with the responder). Immunosuppression included CsA, MMF and methylprednizolone, and was gradually decreased until the end of the first year. The frequency of activated CD4+T (Th) cells recognizing synthetic donor allopeptides corresponding to the hypervariable regions of DRB1 chain from HLA-DR alleles (Inst.of Biochemistry, Univ.of Lausanne) was evaluated in limiting dilution assays (LDA) as has been previously described by Suciu-Focca's group. All samples were also tested for the detection of donor specific alloantibodies using complement dependent lymphocytotoxic method (CDC) in parallel with an Elisa assay (LAT, One Lambda). During the follow-up period 15 patients (50%) exhibited either Th cell alloreactivity against donor peptides but no antibody production (8 pts) or developed donor HLA antibodies against the mm DR and DQ molecules but no allopeptide reactivity (4 pts). Three patients exhibited Th alloreactivity against donor peptides (DR11) and donor specific antibodies (anti-DR11, -DQ2, -DQ7). Three out of 15 patients developed acute rejection (AR) episodes and 4 more patients had graft dysfunction one year post transplantation (Cr>1.9 mg/dl). These preliminary results indicate that during the first year post-Tx and under specific immunosuppression about 50% of the patients exhibit alloreactivity against class II allodeterminants. The definition of the immunogenic alloepitopes in specific donor/recipient pairs in the early stages post-Tx will provide evidence for successful immunointervention.