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. 2020 Jun 1;15(6):e0234090.
doi: 10.1371/journal.pone.0234090. eCollection 2020.

Correlation of increased serum leucine-rich α2-glycoprotein levels with disease prognosis, progression, and activity of interstitial pneumonia in patients with dermatomyositis: A retrospective study

Takaaki Ishida  1 , Takuya Kotani  1 , Satoshi Serada  2 , Minoru Fujimoto  2 , Tohru Takeuchi  1 , Shigeki Makino  1 , Tetsuji Naka  2
Affiliations

Correlation of increased serum leucine-rich α2-glycoprotein levels with disease prognosis, progression, and activity of interstitial pneumonia in patients with dermatomyositis: A retrospective study

Takaaki Ishida et al. PLoS One. .

Abstract

Objective: To investigate whether leucine-rich α2-glycoprotein (LRG) can be a biomarker for the disease activity, progression, and prognosis of interstitial pneumonia (IP) in patients with dermatomyositis (DM).

Methods: Correlations between the clinical findings and serum LRG levels were investigated in 46 patients with DM-IP (33 with acute/subacute IP [A/SIP] and 13 patients with chronic IP [CIP], including 10 fatal cases of IP).

Results: The median serum LRG level of 18.4 (14.6-25.2) μg/mL in DM-IP patients was higher than that in healthy control subjects. The median levels of serum LRG at baseline and at 2 and 4 weeks after the initiation of treatment in the patients who died were significantly higher than those in the surviving patients (P = 0.026, 0.029, and 0.008, respectively). The median level of serum LRG in the DM-A/SIP patients was significantly higher than that in the DM-CIP patients (P = 0.0004), and that in the anti-MDA5-Ab-positive group was slightly higher than that in the anti-ARS-Ab-positive group. The serum LRG levels correlated significantly with the serum levels of LDH, C-reactive protein, ferritin, AaDO2, %DLco, and total ground-glass opacity score. The survival rate after 24 weeks in patients with an initial LRG level ≥ 17.6 μg/mL (survival rate: 40%) was significantly lower than that in patients with an initial LRG level < 17.6 μg/mL (100%) (P = 0.0009).

Conclusion: The serum LRG level may be a promising marker of disease activity, progression, and prognosis in patients with DM-IP.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Serum LRG levels in patients with DM-IP and the HC, and changes in serum LRG levels at baseline measurement and at 2, 4, and 8 weeks after the initiation of treatment.
The serum LRG levels of the DM-IP patients were higher than those of the HC (A). The serum LRG levels at 2, 4, and 8 weeks after the initiation of treatment were significantly decreased in comparison with those before treatment (B). The serum LRG levels at baseline measurement and 2 and 4 weeks after the initiation of treatment were significantly higher in the patients who died than in the surviving patients. The serum LRG levels at 8 weeks after the initiation of treatment were not significantly higher in the patients who died than in the surviving patients because the number of patients was small (C). LRG, leucine-rich α2-glycoprotein; DM, dermatomyositis; IP, interstitial pneumonia; HC, healthy control subjects; NS, not significant. Dashed line: dead due to IP; solid line: alive.
Fig 2
Fig 2. Survival curves of patients with DM-IP based on their serum LRG levels.
The survival rate after 24 weeks in patients with an initial LRG level ≥ 17.6 μg/mL (survival rate: 60%) was significantly lower than that in patients with an initial LRG level < 17.6 μg/mL (100%) (P = 0.0013). Solid line: < 17.6 μg/mL, dashed line: ≥ 17.6 μg/mL (A). The survival rate after 24 weeks in patients with LRG level at 2 weeks after treatment ≥ 8.7 μg/mL (67%) was significantly lower than that in patients with LRG level at 2 weeks after treatment < 8.7 μg/mL (100%) (P = 0.0149). Solid line: < 8.7 μg/mL, dashed line: ≥ 8.7 μg/mL (B). The survival rate after 24 weeks in patients with LRG level at 4 weeks after treatment ≥ 12.5 μg/mL (0%) was significantly lower than that in patients with LRG level at 4 weeks after treatment < 12.5 μg/mL (96.8%) (P = 0.0009). Solid line: < 12.5 μg/mL, dashed line: ≥ 12.5 μg/mL (C). The survival rate after 24 weeks in patients with an initial LRG level ≥ 17.6 μg/mL and that at 2 weeks ≥ 8.7 μg/mL (survival rate: 44%) was significantly lower than that in patients with an initial LRG level < 17.6 μg/mL and/or that at 2 weeks < 8.7 μg/mL (100%) (P < 0.0001). Solid line: an initial LRG level < 17.6 μg/mL and/or that at 2 weeks < 8.7 μg/mL, dashed line: an initial LRG level ≥ 17.6 μg/mL and that at 2 weeks ≥ 8.7 μg/mL (D). Survival rates were calculated by the Kaplan-Meier method and compared by a log-rank test. *P < 0.05. DM, dermatomyositis; IP, interstitial pneumonia; LRG, leucine-rich α2-glycoprotein.
Fig 3
Fig 3. Survival curves using a combination of initial serum LRG and ferritin levels, and AaDO2 level in DM-IP patients.
The survival rate after 24 weeks was 27.3% for the patients with an initial serum level of ferritin ≥ 1005 ng/ml and AaDO2 ≥ 35.6 mmHg. Solid line: Ferritin ≥ 1005 ng/ml and AaDO2 ≥ 35.6 mmHg (A). The survival rate after 24 weeks was 61.5% for the patients with an initial serum level of ferritin ≥ 1005 ng/ml and LRG ≥ 17.6 μg/mL. Solid line: Ferritin ≥ 1005 ng/ml and LRG ≥ 17.6 μg/mL (B). The survival rate after 24 weeks was 33.3% for the patients with an initial AaDO2 ≥ 35.6 mmHg and serum level of LRG ≥ 17.6 μg/mL. Solid line: AaDO2 ≥ 35.6 mmHg and LRG ≥ 17.6 μg/mL (C). The survival rate after 24 weeks was 20.0% for the patients with an initial serum level of ferritin ≥ 1005 ng/ml, AaDO2 ≥ 35.6 mmHg, and initial serum level of LRG ≥17.6 μg/mL. Solid line: Ferritin ≥ 1005 ng/ml and AaDO2 ≥ 35.6 mmHg and LRG ≥ 17.6 μg/mL (D). Survival rates were calculated by the Kaplan-Meier method and compared by a log-rank test. *P < 0.05. DM, dermatomyositis; IP, interstitial pneumonia; LRG, leucine-rich α2-glycoprotein; AaDO2, alveolar-arterial oxygen difference.
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