TNF-α Inhibitors Decrease Classical CD14hiCD16- Monocyte Subsets in Highly Active, Conventional Treatment Refractory Rheumatoid Arthritis and Ankylosing Spondylitis.

Bogdan Batko,Dominik Skiba,Tomasz Mikolajczyk,Mateusz Siedlinski,Agata Schramm-Luc

doi:10.3390/ijms20020291

Abstract

Monocytes are pivotal cells in inflammatory joint diseases. We aimed to determine the effect of TNF-α inhibitors (TNFi) on peripheral blood monocyte subpopulations and their activation in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients with high disease activity. To address this, we studied 50 (32 AS, 18 RA) patients with highly active disease with no prior history of TNFi use who were recruited and assigned to TNFi or placebo treatment for 12 weeks. Cytometric and clinical assessment was determined at baseline, four, and 12 weeks after initiation of TNFi treatment. We observed that treatment with TNFi led to a significant decrease in CD14hiCD16− monocytes in comparison to placebo, while circulating CD14dimCD16+ monocytes significantly increased. The TNFi-induced monocyte subset shifts were similar in RA and AS patients. While the percentage of CD14dimCD16+ monocytes increased, expression of CD11b and CD11c integrins on their surface was significantly reduced by TNFi. Additionally, CD45RA+ cells were more frequent. The shift towards nonclassical CD14dimCD16+ monocytes in peripheral blood due to TNFi treatment was seen in both AS and RA. This may reflect reduced recruitment of these cells to sites of inflammation due to lower inflammatory burden, which is associated with decreased disease activity.

Highlights

The significance of peripheral blood monocytes is increasingly recognized in the pathogenesis of inflammatory joint diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS) [1,2,3]
A decline in the number of classical monocytes was previously reported in a small unrandomized study of 10 (5 RA, 5 AS) patients treated with infliximab, where a rapid decrease in classical monocyte subsets was reported [15]
Aeberli et al suggested that TNF-α inhibitors (TNFi) treatment might restrict monocyte recruitment into inflamed tissues and TNFi-induced apoptosis in peripheral blood monocytes, which was reported earlier [15,16]

Summary

Introduction

The significance of peripheral blood monocytes is increasingly recognized in the pathogenesis of inflammatory joint diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS) [1,2,3]. Puchner et al recently demonstrated in murine models that nonclassical monocytes are crucial in the development of arthritis, literature attributes a role for classical subsets in osteoclast differentiation and joint damage [7,8]. Nonclassical monocytes are selective producers of TNF-α and IL-1β [10] which have been investigated in numerous clinical trials as an effective method to reduce inflammatory disease activity [11,12]. Our goal was to evaluate the effect of anti-TNF-α treatment on peripheral blood monocyte subpopulations, their functional properties, and to compare the effect of treatment in high disease activity, and in conventional treatment-refractory AS and RA patients

Objectives

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Results

Conclusion