INHIBITION OF PHYTOHEMAGGLUTININ-INDUCED LYMPHOPROLIFERATION BY SOLUBLE ANNEXIN-II IN SERA FROM PATIENTS WITH RENAL-CELL CARCINOMA

Annexin II (AII) is a member of a family of glycoproteins which bind n egatively charged phospholipids in a calcium-dependent manner. Annexin s are membrane-associated proteins, expressed both in normal and malig nant cells, but have also been detected as soluble molecules in serum and other body fluids. Because of their adhesive properties, it has be en suggested that annexins play a role in the metastatic process. An E LISA was established for quantification of soluble AII. Within-run var iation was 5.2-10.4% and run-to-run variation 12.4-15.6%. Soluble AII was detected in all sera studied. A strongly positive serum was arbitr arily given the value 100 AII units and used as reference serum. The m ean level in sera from 20 normal blood donors was 49 (SE 5.6) AII unit s. Sera from peripheral blood of five patients with renal cell carcino ma and sera from blood obtained from the renal vein of the same patien ts contained 47 (SE 20) and 83 (SE 28) AII units, respectively. In two patients, AII levels were increased in renal vein serum as compared w ith peripheral blood serum. Interestingly, in both cases, and in none of the three remaining cases, phytohaemagglutinin-stimulated lymphopro liferation was suppressed by renal vein serum as compared with periphe ral blood serum. Affinity absorption of AII from the renal vein sera w ith increased AII levels strongly reduced their immunosuppressive acti vity. Addition of affinity-purified AII to cell cultures suppressed ly mphoproliferation. These data show that the level of AII is markedly i ncreased in renal vein sera from some patients with renal cell carcino ma, suggesting that AII may be locally released in vivo. The study als o demonstrates an immunosuppressive effect of soluble AII in vitro. We speculate that soluble AII released by the tumour has immunosuppressi ve properties. This study identifies soluble AII as a novel immunosupp ressive factor in sera from patients with renal cell carcinoma. A furt her study including a larger number of patients is currently in progre ss, in order to investigate the pathological significance of this find ing.