Background/Purpose: Monocytes represent a heterogeneous circulating population of immune cells that play important roles in the inflammatory response. Two main functional subsets of human monocytes have been identified, as well as their counterparts in mouse. Increasing numbers of reports suggest that each of them exert specific roles in homeostasis and inflammation in vivo, and their involvement in pathological inflammatory responses is growing. The aim of our study was to investigate the effect of the anti-IL6R antibody therapy, in the mouse CIA model and in Rheumatoid arthritis patients, on the frequencies of monocyte sub-populations. 

Methods:

The CIA has been induced by immunization of DBA1 mice with bovine type II collagen. The anti-IL6R antibody (MR16-1) treatment was initiated on day 22 post-immunization using i.p. injections of 0.5mg/mouse twice a week. Blood samples were collected weekly from day 23 and the different monocyte subsets were analyzed by flow cytometry.

15 RA patients were recruited and Tocilizumab was given with approval of the French Drug Agency, in a dose of 8 mg/Kg as a 60-minute intravenous infusion every 4 weeks. For immune monitoring, blood samples from RA patients were collected just before the 1st and 4th tocilizumab infusions (8 mg/Kg).

Results:

Clinical monitoring of CIA showed a stabilization of disease features from day 29 until euthanasia (D44) demonstrating that the anti-IL-6R Ab treatment was able to slowdown CIA progression and decrease disease severity when injected after the boost. We monitored the percentage of monocyte subsets and evidenced fluctuations during clinical course of the disease. The percentage of circulating inflammatory Ly6C^high monocytes was transiently reduced on day 37 in the treated group as compared with controls, while the percentage of the non-inflammatory Ly6C^low monocytes was significantly increased from day 30.

In parallel, we have monitored monocytes cell populations in the blood of RA patients before and during treatment with Tociluzumab and found (1) fluctuations of monocyte subsets following Tociluzumab therapy and (2) significant difference in frequencies in the various subsets before treatment between responders and non-responders and (3) a correlation between clinical benefit and increased frequency of the non-classical CD14^dimCD16⁺ monocytes.

Conclusion: Similar to the increased frequency of the non-classical CD14^dimCD16⁺ monocytes that we observed in the blood from RA patients under Tocilizumab therapy, an increased percentage of their mouse counterpart Ly6C^low monocytes was observed following treatment of CIA mice with MR16-1 Ab. These data suggest new cellular mechanisms insight into clinical benefit associated with anti-IL6R-based therapy and suggest that frequency of the CD14^dimCD16⁺ monocytes can predict clinical response to treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-frequency-of-pratroling-monocytes-in-experimental-arthritis-and-rheumatoid-arthritis-patients-in-response-to-il6-r-blockade/