Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease

Yamakawa, Hideaki; Hagiwara, Eri; Kitamura, Hideya; Yamanaka, Yoshiaki; Ikeda, Satoshi; Sekine, Akimasa; Baba, Tomohisa; Okihara, Koji; Iwasawa, Tae; Takemura, Tamiko; Kuwano, Kazuyoshi; Ogura, Takashi

doi:10.21037/jtd.2017.02.48

Cited by 58 publications

(44 citation statements)

References 32 publications

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“…Although the serum level of SP‐D was a strong predictor of lung fibrosis at baseline, in longitudinal analyses, SP‐D was not predictive of lung fibrosis worsening in most of the analyses. These results are not consistent with those of previous studies , but those earlier studies were small‐sized, diagnosed lung fibrosis by radiography rather than HRCT, included both mixed connective tissue diseases and SSc, and did not perform multivariate analyses.…”

Section: Discussioncontrasting

confidence: 97%

Performance of Candidate Serum Biomarkers for Systemic Sclerosis–Associated Interstitial Lung Disease

Elhaï

Hoffmann‐Vold

Avouac

et al. 2019

Arthritis & Rheumatology

123

140

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Objective. Interstitial lung disease (ILD) in systemic sclerosis (SSc) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for SSc-associated ILD.Methods. Serum samples from a combined cohort of SSc patients (from Paris, France and Oslo, Norway; n = 427) were analyzed by enzyme-linked immunosorbent assay for concentrations of lung epithelial-derived surfactant protein D (SP-D), Krebs von den Lungen 6 glycoprotein (KL-6), CCL18, and OX40 ligand (OX40L). Lung fibrosis was measured by high-resolution computed tomography and pulmonary function tests. Associations of these candidate biomarkers with baseline disease involvement and prediction of disease progression over time (mean ± SD follow-up 3.2 ± 4.4 years) were investigated.Results. In SSc patients at baseline, serum levels of KL-6 correlated with the forced vital capacity (FVC) (r = −0.317, P < 0.001), diffusing capacity for carbon monoxide (r = −0.335, P < 0.001), and extent of lung fibrosis (r = 0.551, P < 0.001). In multivariate analyses, serum levels of KL-6 and SP-D, but not CCL18 and OX40L, were associated with lung fibrosis (odds ratio [OR] 2.41, 95% confidence interval [95% CI] 1.43-4.07 [P = 0.001] and OR 3.15, 95% CI 1.81-5.48 [P < 0.001], respectively). In SSc patients with ILD at baseline, longitudinal, multivariate analyses showed that CCL18 serum levels were an independent predictor of a >10% decrease in the FVC (hazard ratio [HR] 2.90, 95% CI 1.25-6.73; P = 0.014) and de novo development of extensive disease (HR 3.71, 95% CI 1.02-13.52; P = 0.048). Matrix-based logistic regression models for the diagnosis and prognosis of SSc-associated ILD were constructed, and these models discriminated 3 groups of risk (mild, moderate, or high) for the diagnosis or worsening of lung fibrosis according to the serum levels of SP-D (for diagnosis) and serum levels of CCL18 (for progression of disease).Conclusion. These results show that SP-D is a relevant diagnostic biomarker for SSc-associated ILD, whereas KL-6 could be used to assess the severity of lung fibrosis. CCL18 appears to be a potential predictive marker for progression of ILD in SSc.

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Section: Discussioncontrasting

confidence: 97%

Performance of Candidate Serum Biomarkers for Systemic Sclerosis–Associated Interstitial Lung Disease

Elhaï

Hoffmann‐Vold

Avouac

et al. 2019

Arthritis & Rheumatology

123

140

View full text Add to dashboard Cite

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“…Furthermore, the higher levels of BAFF paralleled the higher concentrations of KL‐6 (Fig. b), which has been used as a surrogate marker for evaluation of ILD disease severity . These relationships were not found in those cases whose plasma IFN‐α levels were lower than the cut‐off.…”

Section: Resultsmentioning

confidence: 92%

Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti‐melanoma differentiation‐associated gene 5 dermatomyositis

et al. 2018

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“…In the group of mild lung injury patients, who were with shorter disease course, the predictive effect of KL‐6 on the progression of ILD was more pronounced. Yamakawa et al demonstrated that there was a significant correlation between the changes in serum levels of KL‐6 and the changes in FVC at a median follow‐up interval of 1.9 years in a small size of patients with SSc/mixed connective tissue disease‐associated ILD. Unfortunately, although we found there was a lower degree of correlation between the changes of KL‐6 levels and the changes of TLC% during the follow‐up of 2 years, we did not confirm the relationship between changes in KL‐6 levels and alterations in FVC% and DLCO%.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, as early as 2000, Kenichi Yamane et al found serum levels of Krebs von den Lungen‐6 (KL‐6), a kind of salivary liquefied glycoprotein mainly expressed on the surface of type II alveolar epithelial cells, correlated with SSc‐associated ILD (SSc‐ILD) . The associations between serum KL‐6 and the activity and severity of SSc‐ILD had been explored in some previous studies . In recent years, the value of serum KL‐6 for predicting onset and prognosis of SSc‐ILD has drawn more and more attention.…”

Section: Introductionmentioning

confidence: 99%

Serum levels of Krebs von den Lungen‐6 as a promising marker for predicting occurrence and deterioration of systemic sclerosis‐associated interstitial lung disease from a Chinese cohort

Cao

et al. 2018

Int J of Rheum Dis

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Aim A prospective and longitudinal study to investigate the correlations between Krebs von den Lungen‐6 (KL‐6) serum levels and systemic sclerosis associated with interstitial lung disease (SSc‐ILD). Method Blood samples of baseline and the time point at 2 years follow‐up intervals were collected for the measurement of serum KL‐6 levels. The baseline clinical, laboratory characteristics, and incidence density of newly diagnosed ILD during the follow up were compared between SSc patients with elevated serum KL‐6 levels (KL‐6 > 500 U/mL) and those with normal KL‐6 levels (KL‐6 ≤ 500 U/mL) at baseline. Further, we explored the association between serum KL‐6 and deterioration of ILD measured by lung function parameters during follow‐up of 2 years. Results Patients with elevated baseline serum KL‐6 had a significant tendency to have disappearance of the finger pad. The incidence density of new‐onset ILD in SSc patients with elevated baseline serum KL‐6 and those with normal baseline serum KL‐6 was 1.33% and 0.51%, respectively. Among the mild lung injury group, the incidence density of ILD deterioration in SSc patients with elevated baseline serum KL‐6 and those with normal serum KL‐6 was 1.2% and 0.74%, respectively. Conclusion Serum KL‐6 level correlates with the clinical manifestations of microvascular injury. Baseline elevated serum KL‐6 may predict deterioration of lung function of SSc‐ILD patients with mild lung injury.

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Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease

Cited by 58 publications

References 32 publications

Performance of Candidate Serum Biomarkers for Systemic Sclerosis–Associated Interstitial Lung Disease

Performance of Candidate Serum Biomarkers for Systemic Sclerosis–Associated Interstitial Lung Disease

Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti‐melanoma differentiation‐associated gene 5 dermatomyositis

Serum levels of Krebs von den Lungen‐6 as a promising marker for predicting occurrence and deterioration of systemic sclerosis‐associated interstitial lung disease from a Chinese cohort

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