INCREASED LIVER TRANSPLANT REJECTION WITH A STRONG BUT NOT A WEAK POSITIVE CROSSMATCH

INCREASED LIVER TRANSPLANT REJECTION WITH A STRONG BUT NOT A WEAK POSITIVE CROSSMATCH
JC Scornik, W Van der Werf, A Reed, C Soldevilla Pico, GY Lauwers, and RJ Howard University of Florida College of Medicine, Gainesville, FL.

We reported previously that patients (pts) with a positive crossmatch (XM) did not have increased incidence of liver transplant rejection. While some studies had similar results, others did find an association with either graft loss or rejection. We now report that these discrepancies may be due to the fact that only high antibody (Ab) levels increase the risk of clinically significant rejection. Preformed IgG T and B cell Abs were measured by a 2-color flow cytometry (FC) crossmatch. We previously defined a positive T cell XM as a patient/normal serum ratio of 2 (3 for B cells), and the concentration approaching that needed to fix complement as a ratio of 7 (9 for B cells) (Transplantation 1994, 57:621). In this study a high-titer T or B cell Ab was defined as giving a ratio of >30 or >10 respectively. Pts received standard triple immunosuppression. Rejection was defined by worsening liver function tests and, in almost all cases, confirmed by biopsy. Of 410 pts whose graft functioned for >1 week, the incidence of rejection was similar in Ab negative pts (N=321, 39% at 1 week, 53% at 1 year), T and B positive (N=89, 46% and 57 %), and T positive only (N=51, 45% and 53%). However, pts with high-titer T cell Abs had a higher rejection rate of 60% and 65% (1 week and 1 year), compared with 35% and 45% in low-titer patients (p value not significant, NS). This was confirmed by analyzing the incidence of steroid-resistant rejection (SRR). Such incidence was 8% for patients with no Abs, 12% for patients with T or B cell Abs, and 14% for patients with T cell Abs only (p=NS). However, 7/20 patients (35%) with high-titer T cell Abs had SRR whereas 0/31 patients with low titer T cell Abs had SRR (p<0.0004). The differences for patients with high- or low-titer B cell Abs were not significant. Graft survival (GS) was not impaired in any Ab positive group: actual GS in a 6-year period for all Ab negative patients was 72%, for all Ab positive patients 89%, for high-titer T cell 85% and for low-titer T cell 90%. We conclude that only high-titer donor-specific T cell antibodies are associated with a higher incidence of liver graft rejection. This so far has not led to a detectable increase of graft loss.