4.2 Article

Low-Density Granulocytes and Neutrophil Extracellular Traps as Biomarkers of Disease Activity in Adult Inflammatory Myopathies

Journal

JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
Volume 28, Issue 2, Pages E480-E487

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/RHU.0000000000001772

Keywords

idiopathic inflammatory myopathies; dermatomyositis; NETs; LL-37; low-density granulocytes

Categories

Funding

  1. Colegio Mexicano de Reumatologia (Fondo de Investigacion CMR 2018)
  2. Consejo Nacional de Ciencia y Tecnologia (CONACYT)
  3. Secretaria de Educacion Publica-Ciencia Basica 2017-2018 [A1-S23262]

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This study analyzed the relationship between low-density granulocytes (LDGs), neutrophil extracellular traps (NETs), and clinical and immunological features of patients with idiopathic inflammatory myopathies (IIMs). The results showed that LDGs and NETs containing LL-37 are increased in patients with active disease and correlate with proinflammatory cytokines. Both total and CD10(+) LDGs are potential biomarkers for disease activity and, in combination with NETs, have the potential to detect patients who are at risk for cutaneous ulcers and calcinosis.
Background/Objective Biomarkers for disease activity and damage accrual in idiopathic inflammatory myopathies (IIMs) are currently lacking. The purpose of this cross-sectional study is to analyze the relationship among low-density granulocytes (LDGs), neutrophil extracellular traps (NETs), and clinical and immunological features of patients with IIM. Methods We assessed disease activity, damage accrual, amount of LDGs, NETs, expression of LL-37, and serum cytokines in 65 adult patients with IIM. Differences between groups and correlations were assessed by Kruskal-Wallis, Mann-Whitney U, and Spearman rho tests. The association between LDGs, NETs, disease activity, calcinosis, and cutaneous ulcers was assessed by logistic regression. To address the capacity of LDGs and NETs to diagnose disease activity, we used receiving operating characteristic curves. Results Low-density granulocytes were higher in patients with active disease, ulcers, calcinosis, and anti-MDA5 antibodies, which correlated with serum levels of IL-17A and IL-18. Neutrophil extracellular traps were higher in patients with calcinosis, elevated titers of antinuclear antibodies, and positive anti-PM/Scl75 tests. The combination of a high proportion of both total LDGs and NETs was associated with the presence of calcinosis and cutaneous ulcers. LL-37 was higher in NETs originating from LDGs. Normal-density neutrophils were elevated in patients with active dermatomyositis. Conclusions Low-density granulocytes and NETs containing LL-37 are increased in patients with IIM and active disease, and correlate with proinflammatory cytokines. Both total and CD10(+) LDGs are potential biomarkers for disease activity and, in combination with NETs, have the potential to detect patients who are at risk for cutaneous ulcers and calcinosis.

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