RESEARCH - Preferential decrease of IgG4 anti-CCP antibodies during treatment with TNF blocking agents in patients with RA

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Ann Rheum Dis. Published Online First: 29 April 2008.

doi:10.1136/ard.2008.088401

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Extended Report

Preferential decrease of IgG4 anti-citrullinated protein antibodies

during treatment with TNF blocking agents in patients with rheumatoid

arthritis

Wouter H Bos 1*, Geertje M Bartelds 2, Marijn Vis 3, Ann R van der

Horst 4, Gerrit Jan Wolbink 2, Rob van de Stadt 2, Dirkjan van

Schaardenburg 2, Ben AC Dijkmans 3, Willem F Lems 3, T

Nurmohamed 3, Lucien Aarden 1 and Dorte Hamann 4

1 Sanquin Research, Amsterdam, Netherlands

2 Jan van Breemen Institute, Netherlands

3 VU University medical center, Netherlands

4 Sanquin Diagnostic Services, Amsterdam, Netherlands

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.

http://ard.bmj.com/cgi/content/abstract/ard.2008.088401v1?papetoc

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