| Title | Preferential decrease of IgG4 anti-citrullinated protein antibodies during treatment with TNF blocking agents in patients with rheumatoid arthritis. | | Author(s) | Bos WH, Bartelds GM, Vis M, van der Horst AR, Wolbink GJ, van de Stadt R, van Schaardenburg D, Dijkmans BA, Lems WF, Nurmohamed MT, Aarden L, Hamann D | | Institution | Sanquin Research, Amsterdam, Netherlands. | | Source | Ann Rheum Dis 2008 Apr 29. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18445623 |
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