Expression of 9G4 idiotope on autoantibodies to citrullinated peptides in patients with early inflammatory arthritis and established rheumatoid arthritis

Introduction

The expression of VH4 gene family during immunoglobulin heavy chain synthesis has been detected in autoimmune diseases. In particular, the rat monoclonal antibody 9G4 detects VH4-34-encoded immunoglobulins and B cells expressing these antibodies as surface receptor (autoreactive 9G4+ B cells).

Aim

To determine whether autoantibodies commonly associated with rheumatoid arthritis (RA) express 9G4 idiotope (9G4-Id).

Patients and methods

Serum from 27 patients with established RA and 46 polyarthritis patients (<6 weeks duration) of whom 23/46 were subsequently diagnosed with RA (Early RA, ERA) and 23/46 with other arthritis (Early Non-RA, ENRA) was studied. 9G4-Id detection on anti-CCP, anti-tetanus toxoid (TT), Pneumococcal capsular polysaccharide (PCP) antibodies and total serum IgG and IgM was measured by ELISA.

Results

23/27 patients with established RA had anti-CCP antibodies, 8 of whom had 9G4+ anti-CCP. All were positive for both IgM and IgG anti-CCP. 9G4-Id detection levels correlated more closely with IgM than IgG-CCP. In ERA group, 15/23 patients had anti-CCP and 4/23 had 9G4+ anti-CCP. All 4 patients had both IgM and IgG anti-CCP. In ENRA, only one patient had 9G4+ IgM anti-CCP, albeit at low titer. 9G4-Id was not detected on TT or PCP antibodies.

Conclusion

We describe for the first time the expression of VH4-34 heavy chain gene by autoantibodies to citrullinated peptides early after RA onset. In established RA, the expression of VH4-34 gene by anti-CCP antibodies is positively correlated with their titer, particularly with IgM-CCP. Therefore, we suggest that the expansion of CCP-specific B cell clones may be due to robust expansion of un-switched B cell clones, possibly including those in the splenic marginal zone or their analogous.