Aberrant expansion of circulating CD4+CXCR5+CCR7loPD1hi Tfh precursor cells in idiopathic inflammatory myopathy

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(+) CCR7(lo) PD-1(hi) 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 CCR7(lo) PD-1(hi) 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 CCR7(lo) PD-1(hi) 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 CCR7(lo) PD-1(hi) subsets. IL-21 expression significantly increased in CD4(+) CXCR5(+) CCR7(lo) PD-1(hi) 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 CCR7(lo) PD-1(hi) 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(+) CCR7(lo) PD-1(hi) T cells and intracellular IL-21 decreased significantly when disease was improved (P = .018; P = .028). CONCLUSION: The percentage of circulating CCR7(lo) PD-1(hi) 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.