Background While the emphasis in rheumatoid arthritis (RA) treatment is on early diagnosis and intervention, we cannot provide the certain strategies for diagnosis. It is well known that serum immunoglobulin G (IgG) from RA patient exhibit decreased galactosylation of conservative N-glycans in CH2 domains of the heavy chains. Kondo et al. developed novel high-performance liquid chromatography (HPLC) method for precise analysis of oligosaccharides of IgG1).
Objectives To evaluate both diagnostic and predictive value of agalactosyl IgG in RA, we analyze serum IgG oligosaccharide structures using HPLC both in established RA, and in early undifferentiated arthritis as a diagnostic marker for future development ofRA.
Methods Firstly, serum samples were collected from 94 patients with RA fulfilled the 1987-ACR-criteria, 16 with OA, 18 with SLE, and 24 with healthy subjects (HS). The percentage agalactosyl IgG oligosaccharides (%G0) were analyzed in serum samples by high performance HPLC method. Secondly, we analyzed %G0 in 144 patients with recent-onset undifferentiated arthritis (UA) defined as not fulfilling existing classification criteria. They were studied for whether UA progressed to RA after 2 year.
Results In the first study, serum levels of %G0 were significantly higher in established RA (41.5±9.1) than in HS (21.1±4.4; p<0.01), OA (26.2±7.1; p<0.05), and SLE (28.7±10.4; p<0.05). The second study comprised 144 patients (35 males; 109 females) with early UA. The following parameters were assessed at baseline: %G0, rheumatoid factor (RF), autoantibody to galactose deficient IgG (CARF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 144 patients with early UA, 58 (40.3%) developed RA, 9 (6.2%) developed collagen disease, 33 (22.9%) diagnosed as OA, 21 (14.6%) were UA as ever, and 23 (16.0%) were healthy (transient arthropathy) within two years after registration. %G0 predicted progression of UA to RA with high accuracy (AUC=0.807) at a highest sensitivity of 79.3% among 4 diagnostic markers (Table 1). Moreover, combination of %G0 and ACPA predicted progression of UA to RA with highest accuracy (AUC=0.905; 95% CI, 0.835-0.962).
Conclusions In conclusion, this novel method for analyzing agalactosyl IgG revealed excellent diagnostic value inRA. %G0 as well as ACPA would contribute to prediction of RA, allowing early therapeutic decisions. Furthermore, agalactosyl IgG may be involved in pathogenesis of RA.
Kondo A, et al. Separation of pyridylamino oligosaccharides by high-performance liquid chromatography on an amine-bearing silica column. Anal Biochem 1994, 219, (1), 21-5.
Disclosure of Interest None Declared