Abstracts 95

C-6.4 #177

MULTIPARAMETER MONITORING OF EFFICACY OF OKT3-INDUCED IMMUNE SUPPRESSION IN RENAL ALLOGRAPT RECIPIENTS. M OHMAN, M Kotb, LK Leathers, DK Hathaway, RR Alloway, LW Gaber, and AO Gaber. University of Tennessee, Memphis TN.

A key to successful immunosuppression regimens is thorough immunomonitoring of the efficacy of therapy. Monitoring of renal allograft recipients that received OKT3 immunosuppressive therapy involved measuring daily OKT3 levels and CD3/TCR expression. Development of antibodies to OKT3 was determined on POD9. All patients received OKT3 induction (mean 9.0 days) as part of a quadruple sequential immunosuppressive protocol. Patients received standard (5mg/day, mean cumulative dose 54mg, n=23) and low dose (2mg/day, mean cumulative dose 28.1mg, n=47) therapy. OKT3 dose was increased when needed to maintain CD3 positive cells at <10 or <5%. We studied 42 patients with clearly established outcomes (13 with biopsy proven rejection and 29 with completely normal renal function during the first postoperative month). Repeated low OKT3 levels (<800ng/ml 3 or more times during treatment) were found to increase the risk of early rejection by 9.75 times (p<.018, 95% CI=1.116, 85.16) and repeated elevations of the TCR (>10% 5 or more times during treatment) increased the risk of early rejection by 4.2 times (p<.036, 95% CI=1.054, 16.738). Elevated TCR expression was significantly more common in patients developing anti-OKT3 antibodies. Our data indicate that monitoring single parameters may not be informative, but when several immunological parameters are evaluated simultaneously, the information can be used to adjust therapy and can contribute to successful immunosuppression of allograft recipients.

C-6.4 #178

INTERLEUKIN 6 LEVELS IDENTIFY REJECTION SEVERITY AND STEROID RESISTANCE AMONG CARDIAC ALLOGRAFT RECIPIENTS PM Kimball, B Radovancevic, T Isom, M Metzler, CT Van Buren, OH Frazier, and RH Kerman. University of Texas Medical School, Houston, Texas.

Endomyocardial biopsy (EMBX) is the gold standard for the diagnosis of rejection following cardiac transplantation. However, its invasive nature and cost have resulted in a search for alternative markers of rejection such as changes in Interleukin 6 (IL6) levels. A prospective study of 13 cardiac recipients was undertaken to compare daily serial IL6 levels with weekly EMBX results and clinical outcome. EMBX was scored by the McAlister scale as unremarkable(<4), mild rejection (5) or rejection requiring therapeutic intervention (>6). Patients were followed for 10 months with 100% patient survival. An irrelevant spike in IL6 (260 _+ 140 pg/ml) occurs on POD 2_+ 1 presumably in response to surgical trauma. Unremarkable EMBX ( N = I l) were associated with serum IL6 levels of 17_+ 15 pg/ml. Marginally increased IL6 levels of 45_+7 pg/ml (NS) preceeded mild rejections (N= 10). In contrast, significant elevations (p < 0.001) in IL-6 levels of 197 _+ 50 occurred 2-3 days prior to EMBX scores _>6 (N=15). IL6 levels correlated with clinical response following anti-rejection therapy by steroid bolus in that IL6 levels immediately normalized ( < 20 pg/ml) in 6/6 patients after steroid- responsive rejection. In contrast, steroid-resistant rejections in 4/4 patients were accompanied by immediate post-therapy spiking in IL6 content ( > 197 pg/ml) and increased EMBX score. Serial monitoring of soluble IL6 may facilitate early prediction of severe as well as steroid-resistant rejection among cardiac allograft recipients and, thus, permit earlier therapeutic intervention.