A. Aarli et al., INHIBITION OF PHYTOHEMAGGLUTININ-INDUCED LYMPHOPROLIFERATION BY SOLUBLE ANNEXIN-II IN SERA FROM PATIENTS WITH RENAL-CELL CARCINOMA, APMIS. Acta pathologica, microbiologica et immunologica Scandinavica, 105(9), 1997, pp. 699-704
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.