RELATIONSHIP OF INCREASED LEVELS OF CIRCULATING INTERCELLULAR-ADHESION MOLECULE-1 AFTER HEART-TRANSPLANTATION TO REJECTION - HUMAN-LEUKOCYTE ANTIGEN MISMATCH AND SURVIVAL

Noninvasive methods to assess immune activation would be helpful in op timizing therapy after heart transplantation to reduce rejection (acut e and chronic) and complications caused by excessive immunosuppressive therapy. Intercellular adhesion molecule 1 has been shown to play an important role in T-cell activation and allograft rejection. A soluble form of intercellular adhesion molecule 1 has been discovered to be c irculating in plasma. To test the hypothesis that increased levels of circulating intercellular adhesion molecule 1 may have prognostic valu e as a marker of immune activation, we examined whether levels of circ ulating intercellular adhesion molecule 1 during the early postoperati ve period correlated with endomyocardial biopsy scores, soluble interl eukin-2 receptor levels, human leukocyte antigen mismatch, and surviva l. For the first 3 weeks after surgery, serum was obtained once weekly on the same day as endomyocardial biopsy samples from 52 patients who survived more than 30 days after heart transplantation. A sandwich en zyme-linked immunosorbent assay was used to measure circulating interc ellular adhesion molecule 1 and soluble interleukin-2 receptor. Increa sed circulating intercellular adhesion molecule 1 levels did not corre late with endomyocardial biopsy scores but were associated with greate r mismatch at the human leukocyte antigen-B and -DR loci (p = 0.02). A significant correlation was found (p = 0.002) between circulating int ercellular adhesion molecule 1 levels and soluble interleukin-2 recept or, albeit with a low r value of 0.27. Survival was reduced in patient s with high levels of circulating intercellular adhesion molecule 1 (p = 0.006) or soluble interleukin-2 receptor (p = 0.001) with the great est reduction in survival when both were elevated. This is the first s tudy that has examined whether increased levels of circulating interce llular adhesion molecule 1 after heart transplantation correlate with clinical parameters of immune activation. These initial findings raise the important question of whether noninvasive tests to assess immune activation such as circulating intercellular adhesion molecule 1 and s oluble interleukin-2 receptor could be used clinically to modulate imm unosuppressive therapy or to alter the frequency of endomyocardial bio psy.