Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (6): 1055-1060. doi: 10.19723/j.issn.1671-167X.2021.06.008

Previous Articles     Next Articles

Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury

ZHANG Pu-li1,2,YANG Hong-xia1,2,ZHANG Li-ning1,2,GE Yong-peng1,PENG Qing-lin1,WANG Guo-chun1,LU Xin1,△()   

  1. 1. Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China
    2. Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
  • Received:2021-08-16 Online:2021-12-18 Published:2021-12-13
  • Contact: Xin LU E-mail:luxin_n@163.com
  • Supported by:
    Beijing Municipal Science and Technology Commission(Z191100006619012)

RICH HTML

 10   

PDF (PC)

204

Abstract:

Objective: To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection. Methods: Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn,and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens. Results: A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P<0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P<0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P<0.05). Conclusion: The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

Key words: YKL-40, Dermatomyositis, Anti-MDA5 antibodies, Rapidly progressive interstitial lung disease, Pulmonary infection

CLC Number: 

  • R593.26

Table 1

Comparison of the characteristics of anti-MDA5-positive DM patients with and without pulmonary infection"

Characteristics Total(n=168) With pulmonary infection(n=70) Without pulmonary infection(n=98) P value
Female/male 108/60 43/27 65/33 0.519
Age of onset/years 47.0±11.8 50.5±12.3 45.0±11.2 0.049
Duration/months 4 (2-8) 3 (2-8) 4 (3-9) 0.130
Fever 74 (44.0) 45 (64.3) 29 (29.6) <0.001
Heliotrope rash 90 (53.6) 37 (52.9) 53 (54.1) 0.875
Mechanic hands 74 (44.0) 26 (37.1) 48 (49.0) 0.128
Gottron’s sign 122 (72.6) 51 (72.9) 71 (72.4) 0.953
“v”sign 122 (72.6) 50 (71.4) 72 (73.5) 0.770
Myalgia 65 (38.7) 24 (34.3) 41 (41.8) 0.322
Muscle weakness 102 (60.7) 39 (55.7) 63 (64.3) 0.262
Arthralgia 84 (50.0) 27 (38.6) 57 (58.2) 0.012
ILD 154 (91.7) 68 (97.1) 86 (87.8) 0.030
RP-ILD 66 (39.3) 39 (55.7) 27 (27.6) <0.001
Cough 81 (48.2) 45 (64.3) 36 (36.7) <0.001
Dyspnea 77 (45.8) 41 (58.6) 36 (36.7) 0.005
CK/(IU/L)a 51 (28-107) 49 (27-112) 52 (28-104) 0.892
LDH/(IU/L)b 280 (223-367) 328 (250-437) 257 (203-325) <0.001
CRP/(g/L)c 0.6 (0.3-1.2) 0.85 (0.4-1.7) 0.5 (0.2-0.8) <0.001
ESR/(mm/h)b 21 (13-40) 31.5 (18-58) 18 (11-32) <0.001
PCT/(μg/L)d 0.2 (0.1-0.3) 0.2 (0.1-0.3) 0.1 (0.1-0.3) 0.150
Fet/(μg/L)e 530 (203-1 234) 796.2 (330-1 817) 359 (148-840) <0.001
ALB/(g/L)f 36 (33-39) 36 (30-38) 37 (34-40) 0.016
WBC/(×109/L)c 5.8 (4.1-7.5) 6.4 (4.6-7.8) 5.1 (3.8-7.3) 0.012
Neutrophil/(×109/L)g 4.5 (2.9-6.0) 4.7 (3.4-6.9) 3.8 (2.7-5.5) 0.004
Lymphocyte/(×109/L)h 0.8 (0.5-1.1) 0.7 (0.4-1) 0.9 (0.6-1.2) 0.002
Lymphocyte count/(/μL)i 785 (545-1 122) 480 (409-710) 880 (600-1 360) 0.001
CD3+T cell/(/μL)j 593 (386-871) 364 (321-517) 660 (435-1 048) 0.001
CD4+T/(/μL)j 362 (225-577) 202 (206-299) 414 (272-665) 0.001
Anti-Ro-52-positive, n(%)a 87 (54.4) 43 (64.2) 44 (47.3) 0.035

Figure 1

The serum and BALF levels of YKL-40 among anti-MDA5-positive patients with dermatomyositis complicated with RP-ILD and pulmonary infection A, the serum YKL-40 levels in patients with RP-ILD and non-RP-ILD, and patients with and without pulmonary infection; a, RP-ILD (n=66); b, non-RP-ILD (n=102); c, pulmonary infection (n=70); d, without pulmonary infection (n=98). B, the BALF YKL-40 levels in patients with RP-ILD and non-RP-ILD, and patients with and without pulmonary infection; e, RP-ILD (n=13); f, Non-RP-ILD (n=5); g, pulmonary infection (n=10); h, without pulmonary infection (n=8). C, the serum YKL-40 levels in RP-ILD with pulmonary infection, RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups; i, RP-ILD with pulmonary infection (n=39); j, RP-ILD without pulmonary infection (n=27); k, non-RP-ILD with pulmonary infection (n=31); l, non-RP-ILD without pulmonary infection (n=71)."

Figure 2

Correlation between serum YKL-40 levels and laboratory indicators in anti-MDA5-positive patients with dermatomyositis The serum YKL-40 levels of anti-MDA5-positive DM patients was positively correlated with C reactive protein (A), erythrocyte sedimentation rate (B), ferritin (C), lactate dehydrogenase (D), and inversely correlated with ALB (E), macrophages (F)."

Table 2

Analysis of ROC curve of serum YKL-40 in diagnosing RP-ILD and or pulmonary Infection"

Group Sensitivity%(95%CI) Specificity%(95%CI) AUC(95%CI) Youden index
RP-ILD with pulmonary infection 75 (58-87) 67 (58-75) 0.72 (0.65-0.79) 0.41
RP-ILD without pulmonary infection 37 (19-58) 75 (67-82) 0.54 (0.44-0.65) 0.21
Non-RP-ILD with pulmonary infection 35 (19-55) 79 (68-88) 0.55 (0.45-0.65) 0.14
[1] Gupta R, Kumar S, Gow P, et al. Anti-MDA5-associated dermatomyositis[J]. Intern Med J, 2020, 50(4):484-487.
doi: 10.1111/imj.v50.4
[2] Lian X, Zou J, Guo Q, et al. Mortality risk prediction in amyopathic dermatomysitis associated with interstitial lung disease: The FLAIR model[J]. Chest, 2020, 158(4):1535-1545.
doi: 10.1016/j.chest.2020.04.057
[3] Ge YP, Shu XM, He LR, et al. Infection is not rare in patients with idiopathic inflammatory myopathies[J/OL]. Clin Exp Rheumatol, 2021(2021-07-21)[2021-08-01]. https://pubmed.ncbi.nlm.nih.gov/34369354/.
[4] Wu C, Wang Q, He L, et al. Hospitalization mortality and associated risk factors in patients with polymyositis and dermatomyositis: A retrospective case-control study[J]. PLoS One, 2018, 13(2):e0192491.
doi: 10.1371/journal.pone.0192491
[5] Yeo IJ, Lee CK, Han SB, et al. Roles of chitinase 3-like 1 in the development of cancer, neurodegenerative diseases, and inflammatory diseases[J/OL]. Pharmacol Ther, 2019, 203(2019-07-26)[2021-08-01]. https://doi.org/10.1016/j.pharmthera.2019.107394.
[6] Furuhashi K, Suda T, Nakamura Y, et al. Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis[J]. Respir Med, 2010, 104(8):1204-1210.
doi: 10.1016/j.rmed.2010.02.026 pmid: 20347285
[7] Kornblit B, Hellemann D, Munthe-Fog L, et al. Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis-experience from two prospective cohorts[J]. Immunobiology, 2013, 218(10):1227-1234.
doi: 10.1016/j.imbio.2013.04.010 pmid: 23706599
[8] Spoorenberg SM, Vestjens SM, Rijkers GT, et al. YKL-40, CCL18 and SP-D predict mortality in patients hospitalized with community-acquired pneumonia[J]. Respirology, 2017, 22(3):542-550.
doi: 10.1111/resp.12924 pmid: 27782361
[9] Hozumi H, Fujisawa T, Enomoto N, et al. Clinical utility of YKL-40 in polymyositis/dermatomyositis-associated interstitial lung disease[J]. J Rheumatol, 2017, 44(9):1394-1401.
[10] Jiang L, Wang Y, Peng Q, et al. Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody[J]. Clin Rheumatol, 2019, 38(6):1655-1663.
doi: 10.1007/s10067-019-04457-w pmid: 30739212
[11] Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups[J]. Ann Rheum Dis, 2017, 76(12):1955-1964.
doi: 10.1136/annrheumdis-2017-211468 pmid: 29079590
[12] Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias[J]. Am J Respir Crit Care Med, 2013, 188(6):733-748.
doi: 10.1164/rccm.201308-1483ST
[13] Moghadam-Kia S, Oddis CV, Aggarwal R. Anti-MDA5 antibody spectrum in western world[J]. Curr Rheumatol Rep, 2018, 20(12):78.
doi: 10.1007/s11926-018-0798-1 pmid: 30382445
[14] Sugiyama Y, Yoshimi R, Tamura M, et al. The predictive prognostic factors for polymyositis/dermatomyositis-associated interstitial lung disease[J]. Arthritis Res Ther, 2018, 20(1):7.
doi: 10.1186/s13075-017-1506-7 pmid: 29325580
[15] James AJ, Reinius LE, Verhoek M, et al. Increased YKL-40 and chitotriosidase in asthma and chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2016, 193(2):131-142.
doi: 10.1164/rccm.201504-0760OC
[16] Korthagen NM, van Moorsel CH, Barlo NP, et al. Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis[J]. Respir Med, 2011, 105(1):106-113.
doi: 10.1016/j.rmed.2010.09.012 pmid: 20888745
[17] Fantino E, Gangell CL, Hartl D, et al. Airway, but not serum or urinary, levels of YKL-40 reflect inflammation in early cystic fibrosis lung disease[J/OL]. BMC Pulm Med, 2014, 14: 28[2021-08-01]. https://doi.org/10.1186/1471-2466-14-28.
[18] Wang HL, Hsiao PC, Tsai HT, et al. Usefulness of plasma YKL-40 in management of community-acquired pneumonia severity in patients[J]. Int J Mol Sci, 2013, 14(11):22817-22825.
doi: 10.3390/ijms141122817
[19] Yang X, Sheng G. YKL-40 levels are associated with disease severity and prognosis of viral pneumonia, but not available in bacterial pneumonia in children[J]. BMC Pediatr, 2018, 18(1):381.
doi: 10.1186/s12887-018-1345-y
[20] Long X, Xuan H, Ohshimo S, et al. Serum YKL-40 as predictor of outcome in hypersensitivity pneumonitis[J/OL]. Eur Respir J, 2016, 49(2): 1501924 [2021-08-01]. https://doi.org/10.1183/13993003.01924-2015.
[21] Shirakashi M, Nakashima R, Tsuji H, et al. Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment[J]. Rheumatology (Oxford), 2020, 59(11):3284-3292.
doi: 10.1093/rheumatology/keaa123
[1] Yu-zhou GAN,Yu-hui LI,Li-hua ZHANG,Lin MA,Wen-wen HE,Yue-bo JIN,Yuan AN,Zhan-guo LI,Hua YE. Comparison of clinical and immunological features between clinically amyopathic dermatomyositis and typical dermatomyositis [J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1001-1008.
[2] Jing XU,Jing XU,He LI,Jie TANG,Jian-long SHU,Jing ZHANG,Lian-jie SHI,Sheng-guang LI. Dermatomyositis combined with IgA vasculitis: A case report [J]. Journal of Peking University(Health Sciences), 2019, 51(6): 1173-1177.
[3] Yi-ying YANG,Xiao-xia ZUO,Hong-lin ZHU,Si-jia LIU. Advances in epigenetic markers of dermatomyositis/polymyositis [J]. Journal of Peking University(Health Sciences), 2019, 51(2): 374-377.
[4] YU Jian-feng, JIN Yue-bo, HE Jing, AN Yuan, LI Zhan-guo. Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease associated with dermatomyositis and secondary Sjögren’s syndrome: a case report [J]. Journal of Peking University(Health Sciences), 2017, 49(5): 910-914.
[5] LIU Shuang, AN Yuan, JIA Yuan, LI Zhan-Guo. A case of clinical overlap syndrome of rheumatoid arthritis and amyopathic dermatomyositis with multiple pulmonary injuries [J]. Journal of Peking University(Health Sciences), 2014, 46(5): 805-808.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Author. English Title Test[J]. Journal of Peking University(Health Sciences), 2010, 42(1): 1 -10 .
[2] . [J]. Journal of Peking University(Health Sciences), 2009, 41(2): 188 -191 .
[3] . [J]. Journal of Peking University(Health Sciences), 2009, 41(3): 376 -379 .
[4] . [J]. Journal of Peking University(Health Sciences), 2009, 41(4): 459 -462 .
[5] . [J]. Journal of Peking University(Health Sciences), 2010, 42(1): 82 -84 .
[6] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 319 -322 .
[7] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 333 -336 .
[8] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 337 -340 .
[9] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 225 -328 .
[10] . [J]. Journal of Peking University(Health Sciences), 2007, 39(4): 346 -350 .
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd