XXXVI. The Origin, Variety, Distribution, and Biologic Fate of Connective Tissue Activating Peptide-I11 Isoforms: Characteristics in Patients with Rheumatic, Renal, and Arterial Disease

Objective. To determine the origin, distribution, and biologic fate of platelet-derived connective tissue activating peptid+III (CTAP-111), to define the relative amounts of the antigen forms (CTAP-111, betathromboglobulin [@-TG], neutrophil activating peptide-2 [NAP-21) in plasma of normal persons and those with rheumatic or end-stage renal disease, and to define the isoforms of CTAP-I11 in platelets, plasma, transudates, and tissue deposits. Methods. CTAP-111 in plasma was measured by enzyme-linked immunosorbent assay, and growth promoting activity of CTAP-III isoforms was tested in synovial and peritoneal cell cultures by measuring increased synthesis of ''C-glycosaminoglycan (14C-GAG) and 3HDNA. Isolated CTAP-111 was characterized by Western blotting, microsequencing, and mass spectrometry. Results. CTAP-I11 was the primary isoform of this antigen family in normal platelets and platelet-rich plasma; @-TG and NAP-2 accounted for 4 % of CTAPI11 isoforms. Previously undescribed isoforms, i.e., CTAP-I11 des 1, des 1-2, des 1-3, and a phosphate adduct of CTAP-111, were observed in varying amounts. Elevated plasma levels of CTAP-I11 antigen were found in a substantial fraction of rheumatic disease patieats: 24% of those with rheumatoid arthritis, 36% of those with systemic sclerosis, and 15% of those with systemic lupus erythematosus. All 10 patients with end-stage kidney disease had marked elevations of plasma CTAPI11 levels, which stimulated DNA and GAG synthesis by peritoneal cells in culture. Only large isoforms (such as CTAP-111) were detected in venous plasma of normal subjects, rheumatic disease patients, and patients receiving long-term dialysis. Normal human spleen and kidney contained substantial (pg/gm) amounts of CTAP-I11 and traces of an isoform with the electrophoretic mobility of CTAP-I11 des 1-151NAP-2. Liver, lung, and urine contained lesser (ng/gm) amounts of