PRE AND POST-TRANSPLANT DETECTION OF CLASS I AND CLASS II ANTIBODIES TO PREDICT CARDIAC ALLOGRAFT REJECTION

PRE AND POST-TRANSPLANT DETECTION OF CLASS I AND CLASS II ANTIBODIES TO PREDICT CARDIAC ALLOGRAFT REJECTION.
HM Gebel, SK Takemoto, M Mancini, MR Costanzo, JA Kobashigawa, AL Roggero, JW Ortegal, JM Cecka and AR Tambur. Rush Medical Center, Chicago, IL; UCLA, Los Angeles, CA; and LSU Medical Center, Shreveport, LA.

Screening for panel reactive antibody (PRA) in potential allograft recipients is routinely performed using techniques of complement dependent cytotoxicity (CDC). In this study, a flow cytometric approach was applied to increase the sensitivity of PRA detection. Pre-transplant sera from 94 cardiac allograft recipients (63 males; 31 females) were retrospectively analyzed by both CDC and Flow PRA. By CDC, 7/94 patients (7.4%) had pre-transplant PRA >10%. In contrast, 38/94 patients (40.4%) had pre-transplant anti-HLA antibodies detectable by Flow PRA (13 patients with only class I antibodies; 5 patients with only class II antibodies; 20 patients with both class I and class II antibodies). A highly significant association (p<0.0004) was observed between pre-transplant HLA antibodies detected by Flow PRA and histologically confirmed episodes of vascular and/or cellular rejection occurring within the first year post-transplant. When 62 post-transplant serum specimens from 33 patients were analyzed, we observed that anti-MHC antibodies were detected in 93% of samples (13/14) obtained from patients being treated for rejection but in only 41% (20/48) of samples collected at times when rejection was not occurring (p<0.001). Collectively, our data indicate that detection of pre-and post-transplant PRA by a flow cytometric approach can be of prognostic and diagnostic value to identify patients at risk for rejection. Importantly, the pre-transplant anti-MHC antibodies detected here were generally not directed against donor HLA antigens. Why such antibodies correlate with episodes of rejection is a critical question. We speculate that these preformed antibodies are surrogate markers for T cell responses and that patient T cells are responding to donor derived MHC peptides which share cryptic determinants with those HLA antigens that initially sensitized the patient.