Immunochemical studies on the nature of the serum component (SAA) related to secondary amyloidosis.

Abstract

The relative occurrence of the amyloid-related serum protein SAA in various disease states and in healthy subjects has been compared by both solid phase radioimmunoassay ((RIA) and immunodiffusion techniques which employ antibodies to purified amyloid fibril proten AA of hemogeneous size and charge. SAA levels were elevated above normal in certain categories of neoplastic, inflammatory, and infectious diseases as well as in secondary amyloidosis. The lowest median value, 8 ng./ml., was observed for approximately 150 normal sera, with no age-related increase in subjects ranging in age from 16 to 70 years. The results are consistent with several recent observations that SAA is normal acute phase reactant, and hence the RIA for SAA has no prognostic or diagnostic significance for secondary amyloidosis. The sensitivity of RIA for the detection of SAA is lower than would be expected when AA cross-reactivity values for sera are correlated with their reaction with anti-AA antibodies in immunodiffusion. This observation, along with others reported elsewhere suggests that those determinants which cross-react with anti-AA antibodies are relatively hidden in native SAA. Myeloma sera were less reactive than other groups of pathologic sera in immunodiffusion, although they were similar to other patients' sera when analyzed by RIA. Antibodies to highly purified AA were also used to investigate the structue of SAA by a double-antibody immunoprecipitation method. Precipitated SAA was partially dissociated during sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis to a 12,500 molecular weight moiety designated, SAAL. Multiple radiolabeled species of molecular weight intermidiate to SAA and SAAL were also detected and appeared to represent imcompletely dissociated SAA. The results suggest the SAA is an aggregate of several SAAL chains.