Aberrant expansion of circulating CD4+ CXCR5+ CCR7lo PD1hi Tfh precursor cells in idiopathic inflammatory myopathy

Int J Rheum Dis. 2020 Mar;23(3):397-405. doi: 10.1111/1756-185X.13782. Epub 2019 Dec 27.

Abstract

Objective: To determine circulating follicular T helper (Tfh) cell precursor and its relationship with clinical characteristics in idiopathic inflammatory myopathy (IIM).

Methods: The study population included 47 patients with IIM and 30 healthy controls. Circulating CD4+ CXCR5+ CCR7lo PD-1hi T cells and intracellular interleukin (IL)-21 were assessed by flow cytometry. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay. The disease activity was evaluated using myositis disease activity assessment visual analog scales (VAS) as well as muscle and physician global assessment (PGA).

Results: The percentage of the CCR7lo PD-1hi subset cells within CD4+ CXCR5+ T cells was significantly increased in patients with IIM compared to that in healthy controls (14.3 ± 6.5 vs 11.4 ± 2.6, P = .009). Patients with higher percentages of CCR7lo PD-1hi subsets presented with higher PGA VAS (P = .000), muscle VAS (P = .000), as well as serum creatinine kinase (CK) levels (P = .000) than those with lower percentages of CCR7lo PD-1hi subsets. IL-21 expression significantly increased in CD4+ CXCR5+ CCR7lo PD-1hi T cells in patients with IIM compared to that in healthy controls (26.07 ± 7.38 vs 19.25 ± 5.67, P = .001). Meanwhile, both the CCR7lo PD-1hi subset and intracellular IL-21 expression in IIM patients showed significantly positive correlation with PGA VAS, muscle VAS and serum CK levels. Circulating CD4+ CXCR5+ CCR7lo PD-1hi T cells and intracellular IL-21 decreased significantly when disease was improved (P = .018; P = .028).

Conclusion: The percentage of circulating CCR7lo PD-1hi subset among total CD4+ CXCR5+ T cells and intracellular IL-21 expression expanded and showed significant correlation with disease activity in IIM. The circulating follicular helper T cell precursor may be involved in the pathogenesis, especially muscle injury in IIM.

Keywords: follicular helper T cell; idiopathic inflammatory myopathy; interleukin-21.

MeSH terms

  • Adult
  • Aged
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interleukins / blood
  • Male
  • Middle Aged
  • Myositis / blood
  • Myositis / diagnosis
  • Myositis / immunology*
  • Precursor Cells, T-Lymphoid / immunology*
  • Precursor Cells, T-Lymphoid / metabolism
  • Prognosis
  • Programmed Cell Death 1 Receptor / blood*
  • Receptors, CCR7 / blood*
  • Receptors, CXCR5 / blood*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Young Adult

Substances

  • CCR7 protein, human
  • CXCR5 protein, human
  • Interleukins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CCR7
  • Receptors, CXCR5
  • interleukin-21