Myeloid-derived suppressor cells in axial spondyloarthritis patients with different types of therapy

Abstract

Aim – to evaluate myeloid-derived suppressor cell (MDSC) subset counts and their suppressor potential in axial spondyloarthritis (axSpA) patients, as well as to analyze changes in the studied parameters in biological therapy (BT).Materials and methods. The study included 50 axSpA patients receiving 1st line therapy (non-steroidal anti-inflammatory drugs ±sulfasalazine/methotrexate) and 44 ageand sex-related healthy donors. Eight patients were initiated with BT (TNFαor IL-17 inhibitors). Peripheral blood granulocytic (G-MDSC), monocytic (M-MDSC) MDSCs, early-stage differentiation MDSCs (E-MDSC), and inhibitory molecule expression (PDL1, Arg-1, and IDO) were evaluated by flow cytometry.Results. The axSpA patients were characterized by increased G-MDSC counts (р<0.01), particularly manifested with high disease activity. Axial manifestation was associated with a combination of increased G-MDSC and E-MDSC numbers (р<0.05). The extra-axial group showed an isolated increase in G-MDSC (р<0.05), whereas coxitis was associated with an increase in both G-MDSC and M-MDSC (р<0.05). Low activity was associated with an isolated M-MDSC increase (р=0.045). Patients had reduced expression of majority of the studied suppressor molecules in MDSCs. Axial manifestation was characterized by a decreased expression of PDL1 and IDO in G-MDSCs and E-MDSCs (р<0.05), as well as Arg-1 in E-MDSCs and M-MDSCs (р<0.05). Patients with extra-axial manifestations (including coxitis) exhibited the most significant reduction in the expression of all three inhibitory molecules in M-MDSCs. High activity was associated with a decrease in PDL1+ G-MDSCs and E-MDSCs (р<0.05), as well as Arg-1and IDO-expressing M-MDSCs (р<0.05). In low disease activity, most of the analyzed parameters did not differ significantly from donor values, with the exception of a reduced Arg-1+ M-MDSC frequency (р=0.04). BT reduced G-MDSC counts in 75% of patients to levels comparable to those of healthy donors.Conclusion. Despite the reduced suppressor potential of MDSCs, patients undergoing first-line therapy with high activity demonstrated increased G-MDSC counts, while low activity axSpA was characterized by an isolated increase in M-MDSCs. The BT administration blocked G-MDSC accumulation.

Keywords

• myeloid-derived suppressor cells
• axial spondyloarthritis
• biological therapy
• arginase-1
• indolamine-2
• 3-dioxygenase
• pdl1