Recruitment of immature neutrophils in peripheral blood following leukocytapheresis therapy for rheumatoid arthritis

Abstract

The objective of this study is to evaluate the cellular mechanism underlying filtration leukocytapheresis (LCAP) therapy for the treatment of rheumatoid arthritis (RA). Thirteen patients with refractory RA each underwent three sessions of LCAP. Before (pre-) and after (post-) the completion of the first LCAP session, peripheral blood was sampled and analyzed for neutrophil surface markers using flow cytometry. The surface antigens of peripheral blood mononuclear cells (PBMCs) and neutrophils obtained at pre- and post-LCAP were then analyzed using a fluorescence-activated cell sorter. The American College of Rheumatology's criterion of a 20% improvement was achieved in six patients, but not in the other seven patients, after LCAP therapy. The post-LCAP number of blood band form neutrophils with a bone marrow phenotype (CD49d(dim+), low density) was higher among the responders than among the nonresponders, suggesting an association between the clinical response and the recruitment of bone-marrow-derived neutrophils. After the nonspecific absorption of WBCs during a 1-h Cellsorba procedure, the number of PBMCs was consistently decreased, although the number of neutrophils that were affected by removal plus recruitment varied in a manner that was independent of efficacy. In contrast, the emergence of immature neutrophils in the peripheral blood was characteristic of the effective therapies. These cells were found after the 1st session of responders and also found following sessions of LCAPs. Immature neutrophils, which may be recruited from the bone marrow in the peripheral blood after the first session of LCAP, can predict the clinical efficacy of subsequent LCAP sessions.