Increased circulating serum amyloid A protein derivatives in rheumatoid arthritis patients with secondary amyloidosis.
Secondary amyloidosis, a serious complication of chronic inflammatory diseases, is caused by the deposition of amyloid fibrils in various organs. The major component of amyloid fibrils is derived from serum amyloid A protein (SAA) by proteolysis. To explore the mechanisms of amyloidogenesis, we measured SAA concentrations in the sera of 38 patients with rheumatoid arthritis (RA) without secondary amyloidosis and in the sera of 18 RA patients with secondary amyloidosis, using the latex agglutination immunoassay. We also determined whether SAA was present as a full-length protein in the sera of RA patients by immunoblotting. Although SAA concentrations were elevated in the sera, there were no significant differences in these concentrations between RA patients without amyloidosis (128.2 +/- 145.4 micrograms/ml) and RA patients with amyloidosis (165.0 +/- 162.9 micrograms/ml). To test for qualitative abnormalities of SAA, the isolated SAA proteins from individual RA patients were analyzed by anti-SAA immunoblot. In addition to full-length SAA protein, 6-kd and 4.5-kd SAA-derived fragments were detected in the sera of RA patients, and the ratio of these fragments to total SAA proteins was significantly higher in RA patients with amyloidosis (37.0% +/- 0.7%) compared with that of RA patients without amyloidosis (15.0% +/- 5.5%). Although a high serum level of SAA is a predisposing condition for amyloid formation in RA patients, our data suggest that the increased circulating proteolytic cleavage of SAA may potentially contribute to the development of AA-amyloid deposition.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Tsukada
T
T
Kawabe
Y
Y
Takashima
H
H
Mine
M
M
Aoyagi
T
T
Ichinose
Y
Y
Nagataki
S
S
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000097:blood* / Q000209:etiology*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications*; D002846:Chromatography, Affinity; D005260:Female; D006801:Humans; D007841:Latex Fixation Tests; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D000685:Serum Amyloid A Protein / Q000031:analogs & derivatives
D000685:Serum Amyloid A Protein