Top

Clinical Rheumatology

Published in:

01-06-2019 | Dermatomyositis | Original Article

Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody

Authors: Lili Jiang, Youlian Wang, Qinglin Peng, Xiaoming Shu, Guochun Wang, Xiaomu Wu

Published in: Clinical Rheumatology | Issue 6/2019

Abstract

Objective

We aimed to investigate the clinical value of checking serum chitinase-3-like-1 protein (YKL-40) levels in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5⁺DM) patients.

Methods

One hundred and five consecutive anti-MDA5⁺DM patients and 44 healthy controls were enrolled in this study. Baseline and follow-up serum YKL-40 were detected by ELISA. We evaluated the association of YKL-40 with rapidly progressive interstitial lung disease (RPILD), severity of interstitial lung disease (ILD), and ILD-related survival.

Results

Forty-one out of 105 anti-MDA5⁺DM patients had RPILD at the time of serum sample collection (39.0%). Serum YKL-40 levels were significantly higher in anti-MDA5⁺DM patients with RPILD compared with those without (p = 0.011). One month after treatment, patients with aggravated ILD had increased YKL-40 levels, while those with stable/improved ILD had decreased YKL-40 levels. Higher serum levels of ferritin and YKL-40, as well as lower peripheral CD3⁺T cell counts, were independently associated with poorer prognosis. Kaplan–Meier survival curve showed that the 6 months survival rate in patients with high serum YKL-40 level (> 80 ng/ml) was significantly lower than that in patients with low YKL-40 level (≤ 80 ng/ml) (67% vs 89%, p < 0.01).

Conclusion

YKL-40 can be useful as an indicator for the occurrence of RPILD and correlates with severity of ILD and poor prognosis in anti-MDA5⁺DM patients. Closely monitoring and intensive treatment are suggested in anti-MDA5⁺DM patients showing high level of YKL-40, especially levels > 80 ng/ml.

Chen F, Wang D, Shu X, Nakashima R, Wang G (2012) Anti-MDA5 antibody is associated with a/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis. Rheumatol Int 32(12):3909–3915. https://doi.org/10.1007/s00296-011-2323-y CrossRefPubMed

Sato S, Kuwana M, Fujita T, Suzuki Y (2013) Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol 23(3):496–502. https://doi.org/10.1007/s10165-012-0663-4 CrossRefPubMed

Koga T, Fujikawa K, Horai Y, Okada A, Kawashiri SY, Iwamoto N, Suzuki T, Nakashima Y, Tamai M, Arima K, Yamasaki S, Nakamura H, Origuchi T, Hamaguchi Y, Fujimoto M, Ishimatsu Y, Mukae H, Kuwana M, Kohno S, Eguchi K, Aoyagi K, Kawakami A (2012) The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford, England) 51(7):1278–1284. https://doi.org/10.1093/rheumatology/ker518 CrossRef

Hakala BE, White C, Recklies AD (1993) Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 268(34):25803–25810PubMed

Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang MJ, He CH, Takyar S, Elias JA (2011) Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol 73:479–501. https://doi.org/10.1146/annurev-physiol-012110-142250 CrossRefPubMed

De Ceuninck F, Gaufillier S, Bonnaud A, Sabatini M, Lesur C, Pastoureau P (2001) YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes. Biochem Biophys Res Commun 285(4):926–931. https://doi.org/10.1006/bbrc.2001.5253 CrossRefPubMed

Wang Y, Ripa RS, Johansen JS, Gabrielsen A, Steinbruchel DA, Friis T, Bindslev L, Haack-Sorensen M, Jorgensen E, Kastrup J (2008) YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease. Scand Cardiovasc J 42(5):295–302. https://doi.org/10.1080/14017430802220567 CrossRefPubMed

Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C (2017) Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 33(2). https://doi.org/10.1002/dmrr.2841

Jefri M, Huang YN, Huang WC, Tai CS, Chen WL (2015) YKL-40 regulated epithelial-mesenchymal transition and migration/invasion enhancement in non-small cell lung cancer. BMC Cancer 15:590. https://doi.org/10.1186/s12885-015-1592-3 CrossRefPubMedPubMedCentral

10.

Furuhashi K, Suda T, Nakamura Y, Inui N, Hashimoto D, Miwa S, Hayakawa H, Kusagaya H, Nakano Y, Nakamura H, Chida K (2010) Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med 104(8):1204–1210. https://doi.org/10.1016/j.rmed.2010.02.026 CrossRefPubMed

11.

Hozumi H, Fujisawa T, Enomoto N, Nakashima R, Enomoto Y, Suzuki Y, Kono M, Karayama M, Furuhashi K, Murakami A, Inui N, Nakamura Y, Mimori T, Suda T (2017) Clinical utility of YKL-40 in polymyositis/dermatomyositis-associated interstitial lung disease. J Rheumatol 44(9):1394–1401. https://doi.org/10.3899/jrheum.170373 CrossRefPubMed

12.

Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292(7):344–347. https://doi.org/10.1056/nejm197502132920706 CrossRefPubMed

13.

Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292(8):403–407. https://doi.org/10.1056/nejm197502202920807 CrossRefPubMed

14.

Sontheimer RD (2002) Dermatomyositis: an overview of recent progress with emphasis on dermatologic aspects. Dermatol Clin 20(3):387–408. https://doi.org/10.1016/S0733-8635(02)00021-9 CrossRefPubMed

15.

Collard HR, Collard HR, Moore BB et al (2007) Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 176(7):636–643. https://doi.org/10.1164/rccm.200703-463PP CrossRefPubMed

16.

Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann HJ (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824. https://doi.org/10.1164/rccm.2009-040GL CrossRefPubMedPubMedCentral

17.

DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845CrossRefPubMed

18.

Chupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, Kiener P, Cullen M, Grandsaigne M, Dombret MC, Aubier M, Pretolani M, Elias JA (2007) A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med 357(20):2016–2027. https://doi.org/10.1056/NEJMoa073600 CrossRefPubMed

19.

Mora AL, Torres-Gonzalez E, Rojas M, Corredor C, Ritzenthaler J, Xu J, Roman J, Brigham K, Stecenko A (2006) Activation of alveolar macrophages via the alternative pathway in herpesvirus-induced lung fibrosis. Am J Respir Cell Mol Biol 35(4):466–473. https://doi.org/10.1165/rcmb.2006-0121OC CrossRefPubMedPubMedCentral

20.

Lekkerkerker AN, Aarbiou J, van Es T, Janssen RA (2012) Cellular players in lung fibrosis. Curr Pharm Des 18(27):4093–4102CrossRefPubMed

21.

Mathai SK, Gulati M, Peng X, Russell TR, Shaw AC, Rubinowitz AN, Murray LA, Siner JM, Antin-Ozerkis DE, Montgomery RR, Reilkoff RA, Bucala RJ, Herzog EL (2010) Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype. Lab Invest 90(6):812–823. https://doi.org/10.1038/labinvest.2010.73

22.

Christmann RB, Sampaio-Barros P, Stifano G, Borges CL, de Carvalho CR, Kairalla R, Parra ER, Spira A, Simms R, Capellozzi VL, Lafyatis R (2014) Association of interferon- and transforming growth factor beta-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis. Arthritis Rheum 66(3):714–725. https://doi.org/10.1002/art.38288 CrossRef

23.

Peng QL, Zhang YL, Shu XM, Yang HB, Zhang L, Chen F, Lu X, Wang GC (2015) Elevated serum levels of soluble CD163 in polymyositis and dermatomyositis: associated with macrophage infiltration in muscle tissue. J Rheumatol 42(6):979–987. https://doi.org/10.3899/jrheum.141307 CrossRefPubMed

24.

Enomoto Y, Suzuki Y, Hozumi H, Mori K, Kono M, Karayama M, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suzuki D, Ogawa N, Nakashima R, Mimori T, Iwashita T, Suda T (2017) Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease. Arthritis Res Ther 19(1):9. https://doi.org/10.1186/s13075-016-1214-8 CrossRefPubMedPubMedCentral

25.

Chino H, Sekine A, Baba T, Iwasawa T, Okudela K, Takemura T, Itoh H, Sato S, Suzuki Y, Ogura T (2016) Radiological and pathological correlation in anti-MDA5 antibody-positive interstitial lung disease: rapidly progressive perilobular opacities and diffuse alveolar damage. Intern Med (Tokyo, Japan) 55(16):2241–2246. https://doi.org/10.2169/internalmedicine.55.5774 CrossRef

26.

Sato S, Hirakata M, Kuwana M, Suwa A, Inada S, Mimori T, Nishikawa T, Oddis CV, Ikeda Y (2005) Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 52(5):1571–1576. https://doi.org/10.1002/art.21023 CrossRefPubMed

27.

Matsushita T, Mizumaki K, Kano M, Yagi N, Tennichi M, Takeuchi A, Okamoto Y, Hamaguchi Y, Murakami A, Hasegawa M, Kuwana M, Fujimoto M, Takehara K (2017) Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis. Br J Dermatol 176(2):395–402. https://doi.org/10.1111/bjd.14882 CrossRefPubMed

28.

Fujiki Y, Kotani T, Isoda K, Ishida T, Shoda T, Yoshida S, Takeuchi T, Makino S (2018) Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients. Mod Rheumatol 28(1):133–140. https://doi.org/10.1080/14397595.2017.1318468 CrossRefPubMed

29.

Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, Takagi K, Baba S, Okamoto Y, Ota Y, Yamanaka H (2012) Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford, England) 51(9):1563–1570. https://doi.org/10.1093/rheumatology/kes102 CrossRef

30.

Isoda K, Kotani T, Takeuchi T, Kiboshi T, Hata K, Ishida T, Otani K, Kamimori T, Fujiwara H, Shoda T, Makino S (2017) Comparison of long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia according to autoantibodies: anti-aminoacyl tRNA synthetase antibodies versus anti-melanoma differentiation-associated gene 5 antibody. Rheumatol Int 37(8):1335–1340. https://doi.org/10.1007/s00296-017-3729-y CrossRefPubMed

31.

Xu Y, Yang CS, Li YJ, Liu XD, Wang JN, Zhao Q, Xiao WG, Yang PT (2016) Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis. Clin Rheumatol 35(1):113–116. https://doi.org/10.1007/s10067-015-3139-z CrossRefPubMed

32.

Nara M, Komatsuda A, Omokawa A, Togashi M, Okuyama S, Sawada K, Wakui H (2014) Serum interleukin 6 levels as a useful prognostic predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. Mod Rheumatol 24 (4):633–636. doi:https://doi.org/10.3109/14397595.2013.844390

33.

Kawasumi H, Gono T, Kawaguchi Y, Kaneko H, Katsumata Y, Hanaoka M, Kataoka S, Yamanaka H (2014) IL-6, IL-8, and IL-10 are associated with hyperferritinemia in rapidly progressive interstitial lung disease with polymyositis/dermatomyositis. Biomed Res Int 2014:815245–815246. https://doi.org/10.1155/2014/815245 CrossRefPubMedPubMedCentral

34.

Kobayashi N, Takezaki S, Kobayashi I, Iwata N, Mori M, Nagai K, Nakano N, Miyoshi M, Kinjo N, Murata T, Masunaga K, Umebayashi H, Imagawa T, Agematsu K, Sato S, Kuwana M, Yamada M, Takei S, Yokota S, Koike K, Ariga T (2015) Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis. Rheumatology (Oxford, England) 54(5):784–791. https://doi.org/10.1093/rheumatology/keu385 CrossRef

35.

Gono T, Kawaguchi Y, Ozeki E, Ota Y, Satoh T, Kuwana M, Hara M, Yamanaka H (2011) Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis. Mod Rheumatol 21(2):223–227. https://doi.org/10.1007/s10165-010-0371-x CrossRefPubMed

Title: Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody
Authors: Lili Jiang
Youlian Wang
Qinglin Peng
Xiaoming Shu
Guochun Wang
Xiaomu Wu
Publication date: 01-06-2019
Publisher: Springer London
Keyword: Dermatomyositis
Published in: Clinical Rheumatology / Issue 6/2019
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-019-04457-w

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody

Abstract

Objective

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2019

Established coronary artery disease in systemic sclerosis compared to type 2 diabetic female patients: a cross-sectional study

YouTube as a source of patient information for ankylosing spondylitis exercises

MiR-5571-3p and miR-135b-5p, derived from analyses of microRNA profile sequencing, correlate with increased disease risk and activity of rheumatoid arthritis

The clinical spectrum of Henoch–Schönlein purpura in children: a single-center study

Correction to: Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort

Subclinical synovitis and enthesitis in psoriasis patients and controls by ultrasonography in Saudi Arabia; incidence of psoriatic arthritis during two years

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page