Background/Purpose:

Anti-citrullinated protein antibodies (ACPA) and IgM-Rheumatoid Factor (IgM-RF) are auto-antibodies that can be detected many years before the clinical diagnosis of Rheumatoid Arthritis (RA) [1]. Since ACPA and IgM-RF are known as predictive and prognostic markers of RA, it is conceivable that these antibodies play a pathogenic role in RA. In recent studies we discovered anti-carbamylated protein (anti-CarP) antibodies as a prognostic marker in RA [2]. In addition anti-CarP antibodies are associated with a conversion to RA in patients that suffer from arthralgia [3]. In this study we analyzed whether anti-CarP antibodies can also be detected prior to the onset of the symptoms of RA and which auto-antibody appears first over time.

Methods:

Sera of 79 RA patients obtained prior to the onset of symptoms and 141 age and sex matched controls that were regular blood donors from Amsterdam, The Netherlands, were tested for the presence of anti-carbamylated fetal calf serum (Ca-FCS) antibodies, anti-cyclic citrullinated peptide 2 (CCP2) antibodies and RF-IgM. A median of 5 (IQR 4-6) sequential pre-RA sera, obtained at 1-6 year intervals was available for analysis.

Results:

Anti-CarP antibodies were present in 27% of the serum samples that were drawn just prior to the diagnosis of RA of blood donors compared to 4% of the matched control samples. Anti-CarP antibodies were present in both ACPA positive and ACPA negative patients. Of the 79 individuals that developed RA, 42% were positive for anti-CCP2 antibodies and 25% for IgM RF.

Analysis of the longitudinal samples revealed that anti-CarP antibodies could be detected many years before the onset of symptoms (median 5 years) (Figure 1). Comparing the first appearance of the three autoantibody families revealed that both ACPA and anti-CarP antibodies appear (similarly) earlier in time as compared to IgM-RF.

Conclusion:

Next to ACPA and IgM-RF also the newly identified anti-CarP antibodies appear many years before the onset of clinical symptoms of RA.

1. Nielen MM, et al. Arthritis Rheum. 2004; 50:380-6.

2. Shi J, et al. Proc.Natl.Acad.Sci.U.S.A 2011; 108:17372-7.

3. Shi J, et al.. Arthritis Rheum. 2013; 72(1) 148-50