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. 2022 May 3:9:903887.
doi: 10.3389/fmed.2022.903887. eCollection 2022.

Resistin Expression Is Associated With Interstitial Lung Disease in Dermatomyositis

Lifang Ye  1   2 , Yu Zuo  1 , Fang Chen  1 , Yuetong Xu  1   2 , Puli Zhang  1   3 , Hongxia Yang  1   3 , Sang Lin  1   2 , Qinglin Peng  1 , Guochun Wang  1   2 , Xiaoming Shu  1
Affiliations

Resistin Expression Is Associated With Interstitial Lung Disease in Dermatomyositis

Lifang Ye et al. Front Med (Lausanne). .

Abstract

Objective: In the current study, we aimed to assess resistin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of dermatomyositis patients with interstitial lung disease (DM-ILD) and their correlation with disease activity.

Methods: We detected resistin mRNA levels in the PBMCs of 37 DM-ILD, 8 DM patients without ILD, and 19 healthy control (HC) subjects by performing quantitative reverse transcription real-time polymerase chain reaction analysis. Associations between resistin expression levels and major clinical manifestations, laboratory examinations, and disease activity were also analyzed. In addition, resistin expression in lung specimens from patients with DM-ILD was examined via immunohistochemistry and immunofluorescence.

Results: Resistin mRNA levels in PBMCs were significantly higher in DM-ILD than that in DM patients without ILD and HCs (p = 0.043, 0.014, respectively). Among these DM-ILD patients, the resistin levels were significantly elevated in those with rapidly progressive ILD than in those with chronic ILD (p = 0.012). The resistin mRNA levels in DM-ILD positively correlated with serum alanine aminotransferase (r = 0.476, p = 0.003), aspartate aminotransferase (r = 0.488, p = 0.002), lactate dehydrogenase (r = 0.397, p = 0.014), C-reactive protein (r = 0.423, p = 0.008), ferritin (r = 0.468, p = 0.003), carcinoembryonic antigen (r = 0.416, p = 0.011), carbohydrate antigen 125 (r = 0.332, p = 0.047), interleukin-18 (r = 0.600, p < 0.001), and lung visual analog scale values (r = 0.326, p = 0.048), but negatively correlated with the diffusing capacity of carbon monoxide (DLco)% (r = -0.447, p = 0.041). Immunohistochemical analysis of resistin showed its elevated expression in the macrophages, alveolar epithelial cells, and weak fibrotic lesions from patients with DM-ILD. Immunofluorescence staining confirmed CD68+ macrophages co-express resistin.

Conclusions: Resistin levels were increased in patients with DM-ILD and associated with disease activity and ILD severity. Therefore, resistin may participate in the pathogenesis of DM-ILD and may act as a useful biomarker.

Keywords: dermatomyositis; disease activity; interstitial lung disease; resistin; severity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JZ declared a shared secondary affiliation with the authors LY, YX, SL, and GW at the time of review.

Figures

Figure 1
Figure 1
Resistin mRNA levels were higher from PBMCs in DM patients with ILD than in HCs. (A) Resistin mRNA levels in DM patients with ILD, without ILD, and in HCs. (B) Resistin mRNA levels in patients with DM and RP-ILD or chronic ILD. DM, dermatomyositis; HC, healthy control; ILD, interstitial lung disease; RP-ILD, rapidly progressive interstitial lung disease. The relative resistin expression levels in each group were determined via the 2−ΔCt method. The data shown are expressed as the mean ± SD.
Figure 2
Figure 2
Elevated resistin mRNA levels in PBMCs were associated with laboratory data for patients with DM-ILD. Correlation of resistin mRNA levels in PBMCs with (A) alanine aminotransferase (ALT), (B) aspartate aminotransferase (AST), (C) lactate dehydrogenase (LDH), (D) creatine kinase (CK), (E) C-reactive protein (CRP), (F) ferritin, (G) carcinoembryonic antigen (CEA), (H) carbohydrate antigen (CA)125, and (I) interleukin-18 (IL-18) levels. Correlations were assessed using Spearman's correlation analyses.
Figure 3
Figure 3
Elevated resistin mRNA levels in PBMCs correlated with the severity of lung involvement in DM-ILD. (A) Resistin mRNA levels were negatively associated with the DLco% in patients with DM-ILD. (B) Correlation between resistin mRNA levels and lung VAS values in DM-ILD. DLco, carbon monoxide diffusion capacity; DM-ILD, dermatomyositis-related interstitial lung disease; VAS, visual analog scale.
Figure 4
Figure 4
Correlation between resistin mRNA levels and disease activities in DM-ILD. (A) Correlation between resistin mRNA levels and physician VAS scores. (B) Resistin mRNA levels before and after treatment. (C) Physician VAS scores before and after treatment. Paired analysis was assessed by Wilcoxon's signed-rank test. DM, dermatomyositis; ILD, interstitial lung disease.
Figure 5
Figure 5
Elevated resistin expression in the lung tissue of patients with DM-ILD. (A,B) Lung of healthy control: A small number of resistin–positive macrophages (red arrowhead). Scale bar = 50 μm. (C,D) Lung of patients with DM-ILD: Resistin was strongly expressed in macrophages (red arrowhead), alveolar epithelial cells (blue arrowhead), and weak fibrotic lesions (green arrowhead). Scale bar = 50 μm. (E,F) Lung of patients with DM-ILD: Immunohistochemistry analysis on serial sections using an anti-CD68 antibody confirmed that resistin-positive cells were mostly macrophages (black arrowhead). Scale bar = 50 μm. (G,H) Isotype-matched control antibody for resistin in DM-ILD and HC. Scale bar = 50 μm. (I) Lung of healthy control: Two color immunofluorescence of resistin (red) with CD68+ macrophages (green), DAPI (blue). Scale bar = 50 μm. (J) Lung of patients with DM-ILD: Two color immunofluorescence of resistin (red) with CD68+ macrophages (green). Scale bar = 50 μm. DM, dermatomyositis; ILD, interstitial lung disease; HC, healthy control.
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