Background Rheumatoid arthritis (RA) is a chronic, inflammatory disease, with a risk of secondary amyloidosis development. Amyloidosis is a serious, potentially life-threating disorder resulting in organ dysfunction or failure. Serum amyloid A protein (SAA) is an acute-phase reactant stimulated by pro-inflammatory cytokines and a precursor of amyloid A protein, the fibrillar component of amyloid deposits. Chronically elevated concentration of SAA predicts amyloidosis and is associated with a poor prognosis and a risk of premature death.
Objectives The purpose of the study was to assess an association between SAA concentration and markers of the disease activity as well as metabolic parameters in patients with RA.
Methods The study population consisted of 140 RA patients (111 women, 29 men); with the mean (SD) age 50.3 (10.9) years, disease duration 10.1 (7.5) years. Long-term RA (duration ≥10 years) was noted in 64 patients (45.7%); erosive form of RA in 117 (84%). The mean (SD) disease activity score (DAS28) was 4.5 (1.3); high disease activity (DAS28 ≥5.1) was observed in 42 patients (30%). At least one synthetic disease modifying anti-rheumatic drug (DMARD) was administered in 135 patients: methotrexate (58.6% of all patients), leflunomide, sulfasalazine chloroquine, cyclosporine. Simultaneously therapy with biological DMARD (infliximab, etanercept, rituximab, adalimumab) was used in 36 (25.7%) and low-dose prednisone (≤10 mg/day) in 108 (77%).
Serum concentration of SAA was determined by a commercial enzyme linked-immuno-sorbent assay (ELISA), with the normal reference range <10 mg/l.
Results The mean SAA concentration was 327.0 (263.4) mg/l and was significantly higher in men than in women [433.6 (238) vs 298.9 (264) mg/l, p=0,01]. The normal SAA level was observed only in 9 patients (6.4%). The mean SAA concentration was associated with parameters of disease activity and inflammation. Positive correlations were found between SAA and DAS28, health assessment questionnaire (HAQ) value, swollen and tender joints counts, morning stiffness, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, white blood cell count (WBC) and platelet count. Negative correlations were found between SAA and albumin, hemoglobin, glucose, QTc value. When performing multiple linear regression analysis strong associations were found for CRP, WBC, glucose and QTc.
When assessing women with RA, significantly higher concentrations of SAA were found in patients with high vs low/moderate disease activity [470.7 (242) vs 228.4 (239) mg/l, p<0.001], with presence of atherosclerotic plaques vs no plaques [370 (256) vs 273.4 (263) mg/l, p=0.04], treated with synthetic vs biological DMARDs [332.1 (266) vs 210.2 (237) mg/l, p=0.01] and treated vs not treated with glucocorticoids [330.3 (265) vs 197.3 (236) mg/l, p=0.006]. There were no such correlations in men with RA.
Conclusions Serum concentrations of SAA were above normal in most of RA patients, in spite of moderate/low disease activity assessed with DAS28 and regardless of active DMARDs treatment. The mean SAA concentration was correlated with clinical and laboratory parameters of RA activity. In women higher SAA level was also associated with symptoms of advanced atherosclerosis. Persistently increased SAA concentration may indicate residual chronic inflammatory process, associated with the risk of amyloidosis development.
Disclosure of Interest None Declared