Amyloid Fibril Protein Subunit,‘Protein AS’: Distribution in Tissue and Serum in Different Clinical Types of Amyloidosis Including that Associated with Myelomatosis and Waldenström's Macroglobulinaemia

Abstract

Gel filtration of degraded amyloid fibrils, derived from patients with different clinical types of amyloidosis, revealed a nonimmunoglobulin protein of low molecular weight (protein AS). This protein was previously found in amyloidosis secondary to chronic inflammation. In this study it was also shown to be present in amyloid connected with certain cases of primary amyloidosis and amyloidosis associated with myelomatosis and Waldenström's macroglobulineamia with Bence‐Jones proteinuria. Furthermore, a serum component with electrophoretic mobility in the alpha‐beta‐globulin region and molecular weight of approximately 100,000 was found to be antigenically related to protein AS. This component was found in sera of patients with amyloidosis and also in patients with other diseases known to be associated with amyloidosis. The antigenic cross reactions demonstrated among different amyloid fibrils may be due to protein AS.

A Serum Component Related to Nonimmunoglobulin Amyloid Protein AS, a Possible Precursor of the Fibrils

“…DISCUSSION The nonimmunoglobulin amyloid protein AS with the reported molecular weight of 7,000-9,000 daltons (10,19,20) corresponding to 76 amino acids (20) is shown to be an integral part of the amyloid substance in secondary amyloidosis (8,10,19). In addition, we have recently demonstrated the presence of protein AS in amyloid preparations derived from patients with primary amyloidosis as well as amyloidosis associated with myelomatosis or macroglobulinemia (9,12). It has been shown that protein AS can form fibrils (8,21,22).…”

“…The molecular weight of protein ASC (100,000) is far higher than that of protein AS (9,145) as determined by the total amino acid sequence (20). Levin et al (10) suggested that protein AS is a fragment of a larger protein, since the N-terminal part of the protein in their experiments seemed to be heterogenous.…”

“…In this study, preparations derived from two patients with amyloidosis associated with juvenile rheumatoid arthritis (T. H., amyloid I) and Waldenstr6m's macroglobulinemia (J. B., amyloid XVIII) were used (9,13). For separation of protein AS, the "native" amyloid fibrils (10-20 mg/ml) were treated with 6 M guanidine-HCl in 0.55 M Tris-H-Cl buffer pH 8.5 containing 0.1 M dithiothreitol, or with 0.1 N NaOH for 2-24 h before gel filtration on a 3.2 X 96.5-cm Sephadex G-100 column.…”

“…Recently developed procedures for the isolation and solubilization of amyloid fibrils have enabled the chemical and antigenic characterization of the protein components of amyloid fibrils (4)(5)(6). We reported previously that a nonimmunoglobulin low molecular weight protein AS (amyloid subunit) can be isolated from amyloid fibril preparations derived from patients with different clinical types of amyloidosis involving primary and myeloma/macroglobulinemia-associated as well as secondary amyloidosis (7)(8)(9). Protein AS was thought to be an essential part of amyloid fibrils in most amyloid substances.…”

“A” protein of amyloidosis isolation of a cross‐reacting component from serum by affinity chromatography

“…It has been shown to have 76 amino acid residues in a single chain with a molecular weight of 8500 daltons although minor substitutions have been reported (2). Although this protein was the major constituent of amyloid fibrils isolated from a patient with familial Mediterranean fever (FMF) (2), other investigators have found a smaller percentage in amyloidotic tissues (5,6).…”