Comparison of anti-agalactosyl IgG antibodies, rheumatoid factors, and anti-cyclic citrullinated peptide antibodies in the differential diagnosis of rheumatoid arthritis and its mimics.

OBJECTIVE Anti-agalactosyl IgG antibodies [anti-Gal(0) IgG] have been regarded as a useful serological marker for rheumatoid arthritis (RA). Our aim was to evaluate the clinical usefulness of anti-Gal(0) IgG in the differential diagnosis of rheumatic disorders that mimic RA compared to rheumatoid factors (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP). METHODS Sera were collected from 39 patients with RA, 49 patients with primary Sjögren's syndrome (pSjS), 47 patients with systemic lupus erythematosus (SLE), 65 patients with chronic hepatitis B viral infection (HBV), 68 patients with chronic hepatitis C viral infection (HCV) and 19 normal individuals. RF-IgM was measured by the nephelometeric method, and RF-IgA, anti-Gal(0) IgG and anti-CCP were measured by the respective ELISA assays. RESULTS Anti-Gal(0) IgG titers were remarkably elevated in patients with RA (191.0 +/- 250.8 AU/ml) compared to pSjS (37.9 +/- 42.6 AU/ml), SLE (10.3 +/- 13.6 AU/ml), chronic HBV with (36.1 +/- 38.4 AU/ml) or without rheumatic symptoms (9.6 +/- 19.4 AU/ml), RF(+) chronic HCV without rheumatic symptoms (19.0 +/- 14.8 AU/ml), chronic HCV with rheumatic symptoms (15.2 +/- 17.4 AU/ml) and healthy individuals (2.6 +/- 0.7 AU/ml). The specificity of anti-Gal(0) IgG could be greatly enhanced by elevating the cut-off value from 12 AU/ml to 40 AU/ml (68.6% vs. 85.6%, p < 0.001) without significantly compromising its sensitivity (76.9% vs. 61.5%, p > 0.05). CONCLUSION The serum titer of anti-Gal(0) IgG is much higher in rheumatoid arthritis than in mimicking diseases. The specificity of anti-Gal(0) IgG is enhanced when the cut-off value is raised. However, anti-CCP remains the most specific biomarker for RA.