engleski

HLA FACTORS ASSOCIATED WITH DONORSPECIFIC HLA ANTIBODY DEVELOPMENT IN HEART TRANSPLANTED PATIENTS

Development of HLA donor-specific antibodies (DSA) after heart transplantation (Tx) is one of the indicators for antibody-mediated rejection and can be detrimental to graft and recipient outcomes. We retrospectively analyzed post-Tx DSA monitoring results of 139 heart transplanted patients (median follow-up time 4 yrs) sent to our center in order to investigate possible association of DSA formation detected with mismatched (MM) HLA antigens and MM eplets (defined in HLAMatchmaker algorithm). More than one half of patients (59.7%) tested negative for HLA antibodies and among the rest of the group DSA were defined in 16.6% of cases (DSA+), while remaining 23.7% of patients were positive for non-DSA HLA antibodies. Majority of DSA+ patients had HLA antibodies against DQ antigens (58.6%) with DQ7 as the most prevalent specificity (35.3%) which is in concordance with the most frequent MM antigen HLA- DR11 (25.1%) among DSA+ patients. None of the HLA-DR MM showed statistically significant increased frequency among DSA+ patients and potential association with a higher risk for DSA development. HLAMatchmaker eplet analysis was performed with known HLA-A, -B, -DRB1 typing of patients and donors while majority of HLA-DRB3/4/5, - DQA1 and -DQB1 typing results was presumed based on linkage disequilibrium and population data. HLAMatchmaker HLADR/ DQ total scores ranged from 0-82, with a median of 35 in the entire cohort. The highest number of patients (45.3%) revealed a score within a 31-50 range. Frequency of MM DQ eplets ; 30 (OR 4.21 ; P=0.0092) as well as total number of MM HLA-DR/DQ eplets ; 51 (OR 4.13 ; P=0.0141) was significantly higher among DSA+ patients than in DSA negative patients. This result suggests that amount of MM HLADR/ DQ eplets is a risk factor for DSA development in patients after heart Tx. Since it is usually not possible to avoid DR/DQ MM in heart Tx, this risk factor should be taken into consideration during post-Tx monitoring.

HLA, antibodies, heart transplantation

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