Identification of a natural soluble form of human CD5

CD5 is a 67 kDa type I glycoprotein which belongs to the Scavenger Receptor Cysteine-Rich (SRCR)family of receptors. This family includes either cell- surface (e.g. CD6) or secreted (e.g Sp alpha) proteins implicated in the de velopment of the immune system and the regulation of immune responses. In t his study, we purified and characterised a circulating natural soluble CD5 form (nsCD5) which is indistinguishable (in apparent molecular mass, glycos ylation pattern, and antibody reactivity) from a recombinant soluble CD5 fo rm (rsCD5) composed of the three extracellular SCRC domains. The nsCD5 is a N-glycosylated 52 kDa molecule present in normal human serum and in supern atants of in vitro phorbol ester- and CD3-stimulated peripheral blood monon uclear cells. The nsCD5 concentration in sera from healthy donors is relati vely low (median 1.75 ng/ml, n=166) and is similar to that found in sera fr om patients suffering of various autoimmune (systemic lupus erythematosus, primary Sjogren syndrome, rheumatoid arthritis) and non-autoimmune (chronic renal failure, B-cell chronic lymphocytic leukemia) disorders. In vitro ex periments indicate that nsCD5 is released by proteolytic cleavage of the me mbrane form. These results represent the first evidence of proteolytic rele ase of a transmembrane SRCR family member following cell activation.