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


METHODS
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.


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 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.


CONCLUSIONS
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.
Bos
W H
WH
Sanquin Research, Amsterdam, The Netherlands. w.bos@sanquin.nl
Bartelds
G M
GM
Vis
M
M
van der Horst
A R
AR
Wolbink
G J
GJ
van de Stadt
R J
RJ
van Schaardenburg
D
D
Dijkmans
B A C
BA
Lems
W F
WF
Nurmohamed
M T
MT
Aarden
L
L
Hamann
D
D
D000068879:Adalimumab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D000069285:Infliximab; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D000069285:Infliximab; D000068879:Adalimumab