Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody

Takada, Toshinori; Ohashi, Kazumasa; Hayashi, Masachika; Asakawa, Katsuaki; Sakagami, Takuro; Kikuchi, Toshiaki; Sato, Shinji

doi:10.1016/j.rmed.2018.06.012

Cited by 25 publications

(12 citation statements)

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“…Thus, IL-15 production is also potentially involved in immune responses such as the activation of macrophages and NK cells as well as the function of other biomarkers in patients with PM/DM-RPILD. In line with our findings, nonsurvivors with anti-MDA5 antibodypositive ILD exhibit higher serum IL-15 levels before treatment compared with survivors with anti-MDA5 antibody-positive ILD [29]. Accordingly, these previous reports and the present study support that serum IL-15 is a useful biomarker for predicting the prognosis of patients with PM/DM-RPILD.…”

Section: Discussionsupporting

confidence: 92%

IL‐15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis

et al. 2020

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Background Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. Objectives To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM‐ILD. Methods In total, 49 patients with PM/DM‐ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti‐MDA5 antibody, compared them between the RPILD (n = 23) and non‐RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL‐15 expression in lung tissues. The IL‐15 production was also investigated using A549 and BEAS‐2B cells. Results The RPILD group had significantly higher IL‐15, IL‐1RA, IL‐6, CXCL10, VCAM‐1, anti‐MDA5 antibody and ferritin serum levels than the non‐RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti‐MDA5 antibody, IL‐15, CXCL8, CCL22, IL‐1RA and ferritin were the best combination to distinguish the two groups. IL‐15 and CCL22 were also predictive marker for RPILD development in anti‐MDA5 antibody‐positive patients. Additionally, the RPILD group had significantly high IL‐15 levels in BALF. The lung tissues expressed IL‐15, which increased after cytokine stimulation in the A549 cells. Conclusion This study identified a combination of biomarkers predicting PM/DM‐RPILD progression, and IL‐15 is an important cytokine for predicting RPILD development and reflecting ILD severity.

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Section: Discussionsupporting

confidence: 92%

IL‐15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis

et al. 2020

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“…We believe that aggressive treatment with immunosuppressants might lead to CMV infections. It has been reported that IL-15 was significantly elevated in non-survivors, most of whom had CMV antigenemia [32]. IL-15 is a proinflammatory cytokine, secreted mainly by mononuclear cells following viral infection.…”

Section: Discussionmentioning

confidence: 99%

GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience

Tseng

Wang

et al. 2021

JCM

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Background. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. Methods. We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. Results. A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. Conclusions. Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.

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Section: Discussionmentioning

confidence: 99%

“…This hypothesis is consistent with the poor survival documented in patients with interstitial lung disease associated with clinically amyopathic dermatomyositis who are antimelanoma differentiation-associated gene 5 antibody positive and show an increase in serum IL-10 during their clinical course. 49 The results of this study could alter the treatment strategy for AE-IIPs. Nintedanib 50 is known to suppress the effects of profibrotic cytokines, including VEGF, 51 b-FGF 52 and PDGF.…”

Section: Open Accessmentioning

confidence: 93%

Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin

et al. 2021

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BackgroundAcute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs.MethodsThis study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse.ResultsUnivariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality.ConclusionsA higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome.Trial registration numberUMIN000014969.

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Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody

Abstract: IL-15, as well as IL-10, may play a key role in the progression of the patients with ADM-ILD with anti-MDA-5 antibody positive.

Cited by 25 publications

References 35 publications

IL‐15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis

IL‐15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis

GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience

Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin

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