Serum amyloid-A protein concentration in rheumatoid arthritis and its role in monitoring disease activity.

Abstract

SUMMARY The serum concentrations of serum amyloid-A protein (SAA), C-reactive protein (CRP), and alpha,-acid glycoprotein (alpha,-AGP) have been measured in 185 patients with rheumatoid arthritis. SAA and CRP concentrations correlated well (r=086) both within and above the normal ranges, though SAA showed a greater incremental increase than CRP. All patients with normal SAA levels also had normal CRP and alpha1-AGP concentrations. In contrast, in 40 % of patients with normal CRP and alpha1-AGP concentrations the SAA was raised, sometimes markedly so. The clinical and serological assessments of disease activity in these patients were not significantly different from those with concomitantly raised levels of CRP. These findings suggest that SAA is a more sensitive marker of inflammation than is CRP. The role of the measurement of SAA as a monitor for inflammatory disease activity is discussed.

Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-23

“…It has been detected in the sera and tissues of patients with rheumatoid and Lyme arthritis, multiple sclerosis, systemic lupus erythematosus, and asthma, suggesting its involvement in the development of various autoimmune diseases (60,61). Thus, the IL-23-driven Th-IL-17 cells are essential for mediating tissue destruction and inducing autoimmunity, as seen in rheumatoid arthritis, in which a rise of SAA concentration has been reported (7,30). The IL-23-induced IL-17 production also is involved in leukocyte proliferation, as IL-17 stimulates the production of G-CSF and contributes to granulopoiesis (62).…”

“…Secretion of these APPs by hepatocytes results in a marked increase (up to 1000-fold for SAA; higher for CRP) in their plasma concentrations above the basal level, reaching as high as 80 M or 1 mg/ml for SAA (3,4). The dramatic change in APP production is a clinical marker for inflammatory diseases, including atherosclerosis (5,6), rheumatoid arthritis (7), and Crohn's disease (8). Recent studies have shown that changes in CRP concentration may predict the risk of unstable angina, recurrent coronary heart disease, and other cardiovascular disorders (9,10).…”

Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis

“…In brief, mature human SAA1.1 peptide (residues 1-104) was cloned into a pET30a vector and expressed with ( his6 SAA1) or without (SAA1) an N-terminal histidine (his 6 ) tag in E. coli (BL21) and purified by either a HisTrap HP column (GE Healthcare) or a DEAE column and gel-filtration column. All mutations were generated using a QuikChange Mutagenesis Kit (Qiagen).…”

“…Deposition of the amyloid fibril in secondary amyloidosis (AA amyloid) can lead to progressive loss of splenic and renal functions. The main constituent of AA amyloid is the serum amyloid A protein (SAA), a major acute-phase protein and serum marker for inflammatory diseases (5)(6)(7)(8)(9). Amyloid fibrils are protein aggregates with highly ordered characteristic β-sheet structures (10).…”

Current methods for laboratory diagnosis of rheumatoid arthritis

“…Возможно, повышенная концентрация САА является предиктором развития вторичного амилоидоза у больных РА [138]. Примерные значения нормального содержания САА в сыворотке составляют 5-30 мг/л [139].…”