Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibodies (ACPA) subclasses during anti-TNF treatment in patients with rheumatoid arthritis (RA).
Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on citrullinated fibrinogen (ACF) and IgG1:IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks.
Results: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4:IgG1 ACF ratio in the infliximab cohort. In the adalimumab treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4:IgG1 ratio was reduced by 24% (all percentage values P < 0.05). The decrease in antibody levels was correlated with the clinical response; EULAR good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4:IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels.
Conclusion: ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4:IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on the chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.