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

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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)

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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
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