Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

Sanquin Research, Amsterdam, The Netherlands.
Annals of the rheumatic diseases (Impact Factor: 10.38). 05/2008; 68(4):558-63. DOI: 10.1136/ard.2008.088401
Source: PubMed


To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA).
IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-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.
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 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; European League Against Rheumatism 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.
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 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.

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Available from: Ann R Van der Horst, Dec 17, 2013
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    • "Although we did not find a decrease in IgG1-anti-CCP antibodies, our data indicate an association between the blockade of IL-6R and a reduction in IgG4-specific anti-CCP Abs. Treatment with TNF blocking agents in RA patients has also been reported to preferentially reduce IgG4 isotype anti-citrullinated fibrinogen Abs 41. Although total IgG4 levels also decreased with the treatment, Spearman correlation coefficient statistical analysis showed no correlation between the reduction of IgG4-specific anti-CCP Abs and the reduction in the levels of total IgG4 (rs= -0.09, p= 0.81). "
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