Peripheral expansion of myeloid-derived suppressor cells is related to disease activity and damage accrual in inflammatory myopathies

Rheumatology (Oxford). 2023 Feb 1;62(2):775-784. doi: 10.1093/rheumatology/keac374.

Abstract

Objective: To assess the proportion of myeloid-derived suppressor cells (MDSCs), their expression of arginase-1 and programmed cell death ligand 1 (PD-L1) and their relationship with the clinical phenotype of patients with idiopathic inflammatory myopathies (IIMs).

Methods: We recruited 37 IIM adult patients and 10 healthy donors in Mexico City. We evaluated their clinical features, the proportion of MDSCs and their expression of PD-L1 and arginase-1 by flow cytometry. Polymorphonuclear (PMN)-MDSCs were defined as CD33dim, CD11b+ and CD66b+ while monocytic (M)-MDSCs were CD33+, CD11b+, HLA-DR- and CD14+. Serum cytokines were analysed with a multiplex assay. We compared the quantitative variables with the Kruskal-Wallis and Mann-Whitney U tests and assessed correlations with Spearman's ρ.

Results: Most patients had dermatomyositis [n = 30 (81.0%)]. IIM patients had a peripheral expansion of PMN-MDSCs and M-MDSCs with an enhanced expression of arginase-1 and PD-L1. Patients with active disease had a decreased percentage {median 1.75% [interquartile range (IQR) 0.31-5.50 vs 10.71 [3.16-15.58], P = 0.011} of M-MDSCs and a higher absolute number of PD-L1+ M-MDSCs [median 23.21 cells/mm3 (IQR 11.16-148.9) vs 5.95 (4.66-102.7), P = 0.046] with increased expression of PD-L1 [median 3136 arbitrary units (IQR 2258-4992) vs 1961 (1885-2335), P = 0.038]. PD-L1 expression in PMN-MDSCs correlated with the visual analogue scale of pulmonary disease activity (r = 0.34, P = 0.040) and damage (r = 0.36, P = 0.031), serum IL-5 (r = 0.55, P = 0.003), IL-6 (r = 0.46, P = 0.003), IL-8 (r = 0.53, P = 0.018), IL-10 (r = 0.48, P = 0.005) and GM-CSF (r = 0.48, P = 0.012). M-MDSCs negatively correlated with the skeletal Myositis Intention to Treat Index (r = -0.34, P = 0.038) and positively with IL-6 (r = 0.40, P = 0.045).

Conclusion: MDSCs expressing arginase-1 and PD-L1 are expanded in IIM and correlate with disease activity, damage accrual and serum cytokines.

Keywords: PD-L1; arginase-1; cytokines; idiopathic inflammatory myopathies; infectious damage; myeloid-derived suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginase / genetics
  • Arginase / metabolism
  • B7-H1 Antigen / metabolism
  • Cytokines / metabolism
  • Interleukin-6 / metabolism
  • Myeloid-Derived Suppressor Cells*

Substances

  • Arginase
  • Interleukin-6
  • B7-H1 Antigen
  • Cytokines