Abstract
Background:Myeloid-derived suppressor cells (MDSCs) represent heterogeneous population of immature myeloid cells with immunosuppressive functions. The important role of MDSCs is indicated for cancer, but their role in autoimmune pathology is currently controversial. Considering the clinical heterogeneity of ankylosing spondylitis (AS) and involvement of innate immunity in AS pathophysiology the investigation of the MDSC role in AS is of great interest.Objectives:The aim of our study is to investigate the number of MDSC subsets in AS patients with different clinical manifestations, activity, disease duration, and treatment options and to evaluate the ability of MDSCs to mediate immunosuppressive function in AS patients.Methods:The study included 34 patients with AS. Ankylosing Spondylitis Disease Activity Score (ASDAS) was used to assess disease activity and high activity was determined as ASDAS≥2.1. The frequencies of monocytic (M-MDSC) (HLADR-CD14 +), granulocytic (G-MDSC) (lin-HLADR-CD33+ CD66 +) and early-stage (eMDSC) (lin-HLADR-CD33 + CD66-) MDSCs and biomarkers of MDSCc functional activity including of Arg-1, IDO, PDL1 were determined in the peripheral blood by flow cytometry.Results:We found significant elevation in the frequency of both M-MDSC and G-MDSC in the total group of patients compared to healthy controls (HC) (P=0.00006 and P=0.008 respectively), while eMDSCs did not differ from HC. Analysis of MDSCs populations in patient subgroups showed expansion of G-MDSCs in patients with axial plus peripheral damages (P=0.004), while M-MDSCs were elevated regardless of the presence (P=0.002) or absence (P=0.001) of peripheral manifestations. Moreover, the percentage of M-MDSCs was positively correlated with ASDAS in patients with axial disease only (R=0.8; P=0.03). Patients with low activity of disease demonstrated significant elevation of only M-MDSCs compared with HC (P=0.001). Patients who had high activity of disease had increase in both M-MDSCs and G-MDSCs (P=0.008 and P=0.005 respectively). By comparing the frequency of MDSCs in patient groups with different AS duration we showed increase in percentage of both M-MDSCs and G-MDSCs in patients with relatively short duration of disease (< Me=11.5 years) (P=0.002 and P=0.005 respectively) and elevation in M-MDSCs only in patients with longer AS duration (P=0.0003). Compared with patients receiving conventional therapy (NSAIDs, csDMARDs), patients who received biological agents (TNFα inhibitors) had lower disease activity but despite this showed elevated frequencies of M-MDSCs and PMN-MDSCs, comparable to patients receiving conventional therapy. Of note, M-MDSCs in AS patients had increased expression of PDL-1 and IDO (P=0.04 and P=0.02 respectively) and similar to HC expression of Arg-1. The expression of Arg-1, IDO, PDL1 in patients G-MDSCs did not differ from HC.Conclusion:The data obtained indicate that both M-MDSCs and G-MDSCs are elevated in AS patients. However, the increase of G-MDSCs is associated with peripheral manifestations of AS, high activity, longer duration, and the percentage of M-MDSCs was positively correlated with activity in patients with axial disease only. The unchanged expression of Arg-1, PDL-1 and IDO in G-MDSCs and enhanced expression of PDL-1 and IDO in M-MDSCs suggest MDSCs capacity to mediate immunosuppressive function in AS patients.Disclosure of Interests:None declared
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