MOLECULAR VARIANTS OF BETA(2)-MICROGLOBULIN IN RENAL-INSUFFICIENCY

Many patients with renal insufficiency treated by dialysis for more th an 10 years have tissue deposits of amyloid material containing polyme rized beta(2)-microglobulin (beta(2)m) The mechanisms of beta(2)m poly merization and degradation remain unknown. In biological fluids (serum and urine) from haemodialysis patients and in dialysis fluids from pa tients treated by chronic ambulatory peritoneal dialysis (CAPD), we ha ve characterized different molecular forms of beta(2)m, including prot eolytic split products. beta(2)m isoforms of pI 5.7, 5.3 and 4.5-5.0 w ere isolated from urine and CAPD fluid. The pI 5.3 beta(2)m, but not t he other forms, was recovered both as monomers and as dimers. Such dim ers were also detected in serum from patients but not from healthy con trols. pI 5.3 and 5.7 beta(2)m isoforms were found to be nearly identi cal by mass spectrometry and by their amino acid sequences. The amino acid sequence of the 43 N-terminal amino acids of beta(2)m of pI 5.0 s howed identity with the corresponding region of pI 5.7 beta(2)m. Fragm ents recovered from CAPD fluid were similar to proteolytic fragments g enerated from pure pI 5.7 beta(2)m by incubation in mouse ascitic flui d at acidic pH. Furthermore, pure pI 5.7 beta(2)m was converted into m ore acidic forms of 12 kDa upon incubation in mouse ascitic fluid at a cid pH. beta(2)m dimers found in serum may represent a precursor of am yloid fibrils.