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Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease.
J Rheumatol 2019; 46(8):935-942JR

Abstract

OBJECTIVE

To assess prognostic factors of antimelanoma differentiation-associated gene 5 antibody (anti-MDA5)-positive dermatomyositis/clinically amyopathic DM-associated interstitial lung disease (DM/CADM-ILD) and evaluate the use of serum chitotriosidase, a marker for macrophage activation, as a potential biomarker in anti-MDA5-positive DM/CADM-ILD.

METHODS

This retrospective study included 30 patients with anti-MDA5-positive DM/CADM-ILD. The clinical characteristics and laboratory findings at the time of diagnosis were analyzed. Serum chitotriosidase levels were measured in the 30 patients, in 21 healthy controls, and in 25 patients with anti-aminoacyl-tRNA synthetase antibody-positive (anti-ARS)-polymyositis (PM)/DM/CADM-ILD, and the potential of serum chitotriosidase as a prognostic biomarker in anti-MDA5-positive DM/CADM-ILD was assessed.

RESULTS

The median serum chitotriosidase level in patients with anti-MDA5-positive DM/CADM-ILD was 17.3 ng/ml, which was higher than that in healthy controls and anti-ARS-PM/DM/CADM-ILD (2.0 and 8.9 ng/ml, respectively). Of the 30 patients, 10 died of respiratory failure associated with DM/CADM-ILD deterioration. Cox hazard analysis demonstrated that higher serum chitotriosidase level and lower PaO2 value were significant predictors of a poor outcome. Using optimal cutoff levels according to receiver-operating characteristic curve analyses, chitotriosidase ≥ 23.5 ng/ml, ferritin ≥ 800 ng/ml, and Krebs von den Lungen-6 ≥ 720 U/ml were significantly associated with a poor prognosis. Serum chitotriosidase levels were negatively correlated with PaO2 and percentage predicted forced vital capacity. The survival rate was significantly poorer in patients with high chitotriosidase levels (≥ 23.5 ng/ml) than in those with low chitotriosidase levels (< 23.5 ng/ml).

CONCLUSION

Serum chitotriosidase may be a potential biomarker for predicting a poor prognosis in patients with anti-MDA5-positive DM/CADM-ILD.

Authors+Show Affiliations

From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. fujisawa@hama-med.ac.jp. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine. fujisawa@hama-med.ac.jp.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.From the Second Division, Department of Internal Medicine, and the Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. T. Fujisawa, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Hozumi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; H. Yasui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Inui, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; T. Suda, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31092718

Citation

Fujisawa, Tomoyuki, et al. "Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease." The Journal of Rheumatology, vol. 46, no. 8, 2019, pp. 935-942.
Fujisawa T, Hozumi H, Yasui H, et al. Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease. J Rheumatol. 2019;46(8):935-942.
Fujisawa, T., Hozumi, H., Yasui, H., Suzuki, Y., Karayama, M., Furuhashi, K., ... Suda, T. (2019). Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease. The Journal of Rheumatology, 46(8), pp. 935-942. doi:10.3899/jrheum.180825.
Fujisawa T, et al. Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease. J Rheumatol. 2019;46(8):935-942. PubMed PMID: 31092718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease. AU - Fujisawa,Tomoyuki, AU - Hozumi,Hironao, AU - Yasui,Hideki, AU - Suzuki,Yuzo, AU - Karayama,Masato, AU - Furuhashi,Kazuki, AU - Enomoto,Noriyuki, AU - Nakamura,Yutaro, AU - Inui,Naoki, AU - Suda,Takafumi, Y1 - 2019/05/15/ PY - 2018/11/15/accepted PY - 2019/5/17/pubmed PY - 2019/5/17/medline PY - 2019/5/17/entrez KW - ANTI-MDA5 ANTIBODY KW - CHITOTRIOSIDASE KW - DERMATOMYOSITIS KW - FERRITIN KW - INTERSTITIAL LUNG DISEASE KW - PROGNOSTIC FACTORS SP - 935 EP - 942 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 46 IS - 8 N2 - OBJECTIVE: To assess prognostic factors of antimelanoma differentiation-associated gene 5 antibody (anti-MDA5)-positive dermatomyositis/clinically amyopathic DM-associated interstitial lung disease (DM/CADM-ILD) and evaluate the use of serum chitotriosidase, a marker for macrophage activation, as a potential biomarker in anti-MDA5-positive DM/CADM-ILD. METHODS: This retrospective study included 30 patients with anti-MDA5-positive DM/CADM-ILD. The clinical characteristics and laboratory findings at the time of diagnosis were analyzed. Serum chitotriosidase levels were measured in the 30 patients, in 21 healthy controls, and in 25 patients with anti-aminoacyl-tRNA synthetase antibody-positive (anti-ARS)-polymyositis (PM)/DM/CADM-ILD, and the potential of serum chitotriosidase as a prognostic biomarker in anti-MDA5-positive DM/CADM-ILD was assessed. RESULTS: The median serum chitotriosidase level in patients with anti-MDA5-positive DM/CADM-ILD was 17.3 ng/ml, which was higher than that in healthy controls and anti-ARS-PM/DM/CADM-ILD (2.0 and 8.9 ng/ml, respectively). Of the 30 patients, 10 died of respiratory failure associated with DM/CADM-ILD deterioration. Cox hazard analysis demonstrated that higher serum chitotriosidase level and lower PaO2 value were significant predictors of a poor outcome. Using optimal cutoff levels according to receiver-operating characteristic curve analyses, chitotriosidase ≥ 23.5 ng/ml, ferritin ≥ 800 ng/ml, and Krebs von den Lungen-6 ≥ 720 U/ml were significantly associated with a poor prognosis. Serum chitotriosidase levels were negatively correlated with PaO2 and percentage predicted forced vital capacity. The survival rate was significantly poorer in patients with high chitotriosidase levels (≥ 23.5 ng/ml) than in those with low chitotriosidase levels (< 23.5 ng/ml). CONCLUSION: Serum chitotriosidase may be a potential biomarker for predicting a poor prognosis in patients with anti-MDA5-positive DM/CADM-ILD. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/31092718/Clinical_Significance_of_Serum_Chitotriosidase_Level_in_Anti_MDA5_Antibody_positive_Dermatomyositis_associated_Interstitial_Lung_Disease_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&amp;pmid=31092718 DB - PRIME DP - Unbound Medicine ER -