RHEUMATOID-ARTHRITIS EXHIBITS REDUCED ACUTE-PHASE AND ENHANCED CONSTITUTIVE SERUM AMYLOID A PROTEIN IN SYNOVIAL-FLUID RELATIVE TO SERUM - ACOMPARISON WITH C-REACTIVE PROTEIN

Objective. There are 2 classes of serum amyloid A (SAA) protein, acute phase (A-SAA) and constitutive (C-SAA). Hepatic synthesis of A-SAX is dramatically upregulated by inflammatory cytokines, while C-SAA is co nstitutively produced in the absence of inflammation. A-SAA has been s hown to attract monocytes, neutrophils, and T lymphocytes, but the fun ction of C-SAA remains to be determined. SAA proteins have been found in both serum and synovial fluid (SF) of patients with rheumatoid arth ritis (RA), but have not been characterized with respect to isoform di stribution. We determined the relative distribution of A-SAA and C-SAA in serum and SF of patients with RA and compared their abundance to t he classic acute phase response protein, C-reactive protein (CRP). Met hods. A-SAA (isoforms SAA(1), SAA(2)) and CRP were measured by commerc ially available ELISA kits. ELISA were developed for C-SAA (SAA(4)) an d apolipoprotein AI (apo AI) in paired serum and SF from 56 patients w ith RA. Results, Concentrations (mean +/- SD) of A-SAA (SAA(1,2)) in s erum and SF are 124 +/- 247, 20 +/- 32 mu g/ml; CRP 75 +/- 70, 33 +/- 37 mu g/ml; C-SAA (SAA(4)) 106 +/- 49, 91 +/- 39 mu g/ml; and apo AI 1 .19 +/- 0.32, 0.37 +/- 0.12 mg/ml, respectively. CRP correlated positi vely with A-SAA In serum or SF and negatively with apo AI in serum. Th ere was no correlation with apo AI in SE In contrast, there was no cor relation between C-SAA and CRP, A-SAA, or apo AI in serum or in SF. Me dian concentrations of A-SAA in serum and SF (44, 10 mu g/ml) and CRP (46, 20 mu g/ml), respectively. markedly differed from the mean values , whereas median concentrations of C-SAA (104, 85 mu g/ml) and apo AI (1.17, 0.37 mg/ml), respectively, did not. Conclusion, C-SAA concentra tions vary in serum and SF independently of X-SAA and CRP levels. The lower concentration of A-SAX relative to C-SAA and CRP in SF suggests that A-SAA could be selectively catabolized in SF or alternatively not well transported into the synovial space.