TY - JOUR
T1 - RF positivity has substantial influence on the peripheral memory B-cell compartment and its modulation by TNF inhibition
AU - Roll, P.
AU - Muhammad, K.
AU - Schumann, M.
AU - Kleinert, S.
AU - Tony, H. P.
N1 - Funding Information:
We thank A Koss-Kinzinger and I Kuntzsch for technical assistance. This work was supported by an unrestricted grant from Pfizer GmbH.
PY - 2012/5
Y1 - 2012/5
N2 - Objectives: The role of B cells in rheumatoid arthritis (RA) has been well established with the advent of B-cell targeted therapies. Alterations of peripheral B-cell subsets in RA and heterogeneous modulations of the B-cell compartment under tumour necrosis factor (TNF) inhibition have been described. In this study we examined the influence of rheumatoid factor (RF) positivity on the peripheral B-cell compartment and its modulation under TNF blockade. Methods: Consecutive patients with RA and inadequate response to methotrexate (MTX) were stratified according to RF status and a subset of them was included in a prospective study of weekly etanercept treatment. Results: At baseline, RF-negative patients had a significant higher percentage of overall CD27 B cells compared to healthy controls (HC) and RF-positive patients. In detail, RF-negative patients had 46.6 (range 15.786.8) CD27 B cells compared to 31.3 (12.956.9, p 0.026) in HC and 29.8 (1973.3, p 0.04) in RF-positive patients. Within the CD27 compartment, CD27/immunoglobulin (Ig)D memory B cells were significantly increased to 26.4 (range 5.954.7) in RF-negative patients compared to 14.9 (4.127.3, p 0.006) in HC and 10.5 (3.441.1, p 0.003) in RF-positive patients. During anti-TNF therapy, memory B cells increased significantly in relative and absolute numbers only in RF-negative patients. Conclusions: In RF-negative patients, we observed an enhanced frequency of peripheral memory B cells and an accumulation of pre-switch memory B cells. During anti-TNF therapy, memory B cells increased significantly only in RF-negative patients, suggesting that the peripheral memory B-cell compartment is more amenable to TNF inhibition in these patients.
AB - Objectives: The role of B cells in rheumatoid arthritis (RA) has been well established with the advent of B-cell targeted therapies. Alterations of peripheral B-cell subsets in RA and heterogeneous modulations of the B-cell compartment under tumour necrosis factor (TNF) inhibition have been described. In this study we examined the influence of rheumatoid factor (RF) positivity on the peripheral B-cell compartment and its modulation under TNF blockade. Methods: Consecutive patients with RA and inadequate response to methotrexate (MTX) were stratified according to RF status and a subset of them was included in a prospective study of weekly etanercept treatment. Results: At baseline, RF-negative patients had a significant higher percentage of overall CD27 B cells compared to healthy controls (HC) and RF-positive patients. In detail, RF-negative patients had 46.6 (range 15.786.8) CD27 B cells compared to 31.3 (12.956.9, p 0.026) in HC and 29.8 (1973.3, p 0.04) in RF-positive patients. Within the CD27 compartment, CD27/immunoglobulin (Ig)D memory B cells were significantly increased to 26.4 (range 5.954.7) in RF-negative patients compared to 14.9 (4.127.3, p 0.006) in HC and 10.5 (3.441.1, p 0.003) in RF-positive patients. During anti-TNF therapy, memory B cells increased significantly in relative and absolute numbers only in RF-negative patients. Conclusions: In RF-negative patients, we observed an enhanced frequency of peripheral memory B cells and an accumulation of pre-switch memory B cells. During anti-TNF therapy, memory B cells increased significantly only in RF-negative patients, suggesting that the peripheral memory B-cell compartment is more amenable to TNF inhibition in these patients.
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U2 - 10.3109/03009742.2011.645056
DO - 10.3109/03009742.2011.645056
M3 - Article
C2 - 22400711
AN - SCOPUS:84860591346
SN - 0300-9742
VL - 41
SP - 180
EP - 185
JO - Scandinavian Journal of Rheumatology
JF - Scandinavian Journal of Rheumatology
IS - 3
ER -