RF positivity has substantial influence on the peripheral memory B-cell compartment and its modulation by TNF inhibition

Abstract

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 15.7–86.8%) CD27+ B cells compared to 31.3% (12.9–56.9%, p = 0.026) in HC and 29.8% (19–73.3%, 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 5.9–54.7%) in RF-negative patients compared to 14.9% (4.1–27.3%, p = 0.006) in HC and 10.5% (3.4–41.1%, 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.

Acknowledgements

We thank A Koss-Kinzinger and I Kuntzsch for technical assistance. This work was supported by an unrestricted grant from Pfizer GmbH.