Abnormally increased low-density granulocytes in peripheral blood mononuclear cells are associated with interstitial lung disease in dermatomyositis

Zhang, Sigong; Shen, Hongfang; Shu, Xi; Peng, Qinglin; Wang, Guochun

doi:10.1080/14397595.2016.1179861

Cited by 32 publications

(28 citation statements)

References 23 publications

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“…This probably happens because it suppresses the immune response allowing mycobacterium growth. In severe asthma [15] and in interstitial lung disease in dermatomyositis [16], similar to what was described in autoimmune diseases like SLE and RA, the LDG acts worsening the pathologic condition.…”

Section: Neutrophil Subtypes Generated In Specific Conditionssupporting

confidence: 53%

Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions

Perobelli¹,

Silva²,

AdrianaBonomo³

2017

Role of Neutrophils in Disease Pathogenesis

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It is now known that neutrophils make up a population of complex cells with great plasticity, challenging the old view of neutrophil association with tissue damage and early phases of infection. Here, we discuss different contexts in which these cells can induce anti-inflammatory responses. Although distinct surface markers and cytokines profiles were shown, the most reliable characterization of suppressor neutrophil subtypes relies on their functional characteristics. One important example of inhibitory neutrophils generation comes from in vivo treatment with G-CSF, for 5 days, as for hematopoieticstem-cell-transplantation (HSCT). In this case,donor blood is enriched in degranulated granulocytes harboring a functional regulatory phenotype, characterized by IL-10 production. These cells, when transferred together with HSCT, are able to reduce graft-versus-host-disease, being influenced by Treg cells and influencing them back. Importantly, this protection is long lasting and specific, keeping immunocompetence to other antigens. This regulation is paramount in HSCT, and represents a simple approach to be applied in humans. In summary, we discuss the interaction of neutrophils with other cell types and its consequence in immunomodulation. We believe these features confer an important bridge between innate and adaptive immune system, building a new knowledge for an underestimated cell type.

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Section: Neutrophil Subtypes Generated In Specific Conditionssupporting

confidence: 53%

Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions

Perobelli¹,

Silva²,

AdrianaBonomo³

2017

Role of Neutrophils in Disease Pathogenesis

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show abstract

“…Recent evidence shows that neutrophils are actively involved in both innate and adaptive immunity, and play an important pathogenetic role in many autoimmune diseases. Although the role of neutrophils in IIM has not been deeply investigated, patients with PM/DM have an increased number of low density granulocytes (LDCs), a proinflammatory subtype of human neutrophils, in peripheral blood [ 47 ]. In addition, patients with PM/DM-associated ILD have significantly an enhanced formation of neutrophil extracellular traps, and the decreased degradation of neutrophil extracellular traps can directly prime T cells [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Baseline peripheral blood neutrophil-to-lymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: A retrospective observational study

Hur

et al. 2018

PLoS ONE

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Recent studies have suggested that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) are emerging markers of disease activity and prognosis in patients with chronic inflammatory diseases, cardiovascular diseases, or malignancies. Therefore, we investigated the clinical significance and prognostic value of the NLR and CAR in adult patients with polymyositis and dermatomyositis. The medical records of 197 patients with newly diagnosed polymyositis/dermatomyositis between August 2003 and November 2016 were retrospectively reviewed. Survival and causes of death were recorded during an average 33-month observational period. Clinical and laboratory findings were compared between survivors and non-survivors. Using receiver operating characteristic curves, the NLR and CAR cut-off values for predicting survival were calculated. Univariate and multivariate analyses using Cox proportional hazard models were performed to identify factors associated with survival. Twenty-six patients (13.2%) died during the study period, and the 5-year survival-rate was estimated to be 82%. The non-survivor group exhibited older age and a higher prevalence of interstitial lung disease (ILD), acute interstitial pneumonia, and acute exacerbation of ILD compared to that in the survivor group. NLR and CAR values were significantly higher in the non-survivors and in patients with polymyositis/ dermatomyositis-associated ILD, and the death rates increased across NLR and CAR quartiles. Furthermore, when stratified according to the NLR or CAR optimal cut-off values, patients with a high NLR (>4.775) or high CAR (>0.0735) had a significantly lower survival rate than patients with low NLR or CAR, respectively. In addition, old age (>50 years), the presence of acute interstitial pneumonia, hypoproteinemia (serum protein <5.5 g/dL), and high NLR (but not high CAR) were independent predictors for mortality. The results indicate PLOS ONE | https://doi.org/10.1371/journal.pone

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“…The authors also reported a higher percentage of low-density granulocytes (LDGs) along with enhanced NET-formation capabilities in patients with DM as compared with healthy controls, and that this percentage was also higher in DM patients with ILD than in those without. Additionally, LDG percentage was positively correlated with lung disease activity scores [ 30 ]. In line with these reports, the present results showed that increased HNP levels in the plasma and BALF from patients with myositis-associated ILD suggested that neutrophils are likely to release NETs, including HNPs, which are difficult to degrade in patients with myositis-associated ILD.…”

Section: Discussionmentioning

confidence: 99%

Elevated α-defensin levels in plasma and bronchoalveolar lavage fluid from patients with myositis-associated interstitial lung disease

et al. 2018

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BackgroundInterstitial lung disease (ILD) is a prognostic indicator of poor outcome in myositis. Although the pathogenesis of myositis-associated ILD is not well understood, neutrophils are thought to play a pivotal role. Neutrophils store azurophil granules that contain defensins, which are antimicrobial peptides that regulate the inflammatory response. Here, we evaluated levels of the human neutrophil peptides (HNPs) α-defensin 1 through 3 in patients with myositis-associated ILD to determine whether HNPs represent disease markers and play a role in the pathogenesis of myositis-associated ILD.MethodsHNP levels were measured in the plasma and bronchoalveolar lavage fluid (BALF) of 56 patients with myositis-associated ILD and 24 healthy controls by enzyme-linked immunosorbent assay.ResultsAnalysis revealed significantly higher HNP levels in plasma and BALF samples from patients with myositis-associated ILD as compared to those of healthy controls; however, plasma HNPs were significantly correlated with total cell counts in BALF. Additionally, BALF HNP levels were positively correlated with serum surfactant protein-A and the percentage of neutrophils in BALF, and BALF HNP levels correlated with the percentage of reticular opacities in high-resolution computed tomography results for patients with anti-aminoacyl-tRNA synthetase (ARS) antibody positive myositis-associated ILD. Survival did not differ between patients with higher and lower levels of plasma and BALF HNPs.ConclusionsPlasma and BALF HNPs might reflect the disease activities of myositis-associated ILD, especially in patients with anti-ARS antibody positive myositis-associated ILD. However further studies are necessary to clarify whether HNPs represent disease markers and play roles in disease pathogenesis.

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Abnormally increased low-density granulocytes in peripheral blood mononuclear cells are associated with interstitial lung disease in dermatomyositis

Abstract: The abnormal increase of LDGs may exacerbate abnormal NET regulation and further contribute to the pathogenesis of ILD in DM patients by abnormally forming NETs.

Cited by 32 publications

References 23 publications

Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions

Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions

Baseline peripheral blood neutrophil-to-lymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: A retrospective observational study

Elevated α-defensin levels in plasma and bronchoalveolar lavage fluid from patients with myositis-associated interstitial lung disease

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