CIRCULATING SOLUBLE CR-1 (CD35) - SERUM LEVELS IN DISEASES AND EVIDENCE FOR ITS RELEASE BY HUMAN-LEUKOCYTES

C receptor type 1 (CR1, CD35) is present in a soluble form in plasma ( sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum co ncentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and wa s identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p < 0. 0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p < 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/ - 24.0 ng/ml (p < 0.001) in nine patients who underwent liver transpla ntation, and was 33.5 +/- 7.3 in 10 patients with functioning renal gr afts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (>47 ng/ml), which incl uded B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and c hronic myeloproliferative syndromes (4/5). By contrast, no increase wa s observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 d ecreased rapidly after chemotherapy. The mean concentration of sCR1 wa s not significantly modified in 181 HIV-infected patients at various s tages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with ac tive SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p < 0.0 001, and r = 0.60, p < 0.03 respectively). In vitro, monocytes, lympho cytes, and neutrophils were found to release sCR1 into culture superna tants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCRI levels correlated wit h those of human IgG (r = 0.97, p < 0.0001), suggesting synthesis of s CR1 by the transferred lymphocytes. The mechanisms underlining the inc reased levels of sCR1 and its biologic consequences remain to be defin ed.