Serum KL‐6 level is a prognostic marker in patients with anti‐MDA5 antibody‐positive dermatomyositis associated with interstitial lung disease

Abstract

Objective This study aimed to investigate the clinical significance of Krebs von den Lungen‐6 (KL‐6) serum levels in patients with anti‐MDA5 antibody‐positive dermatomyositis (anti‐MDA5+ DM) having interstitial lung disease (ILD), especially in the amyopathic DM phenotype. Methods The serum KL‐6 level was measured using a chemiluminescence enzyme immunoassay (CLEIA) in patients with anti‐MDA5+ DM, including clinically amyopathic dermatomyositis (CADM)‐ILD and classic DM‐ILD, and healthy donors. The baseline and post‐treatment serum KL‐6 levels were determined in 39 patients with CADM‐ILD who experienced remission or acute exacerbation. The association between laboratory findings, high‐resolution computed tomography (HRCT) scores, pulmonary function tests (PFTs), and the predictive value of baseline KL‐6 level for death was analyzed. Results The serum KL‐6 levels were significantly higher in patients with CADM‐ILD (1339 ± 1329 U/mL) compared with DM‐ILD (642.3 ± 498.4 U/mL) and healthy donors (162.4 ± 54.01 U/mL). The KL‐6 levels correlated positively with chest HRCT scores, serum lactate dehydrogenase, serum ferritin levels, and PFTs, but not with erythrocyte sedimentation rate. During follow‐up, the post‐treatment serum KL‐6 levels significantly reduced in the remission/stable group, but increased in the acute exacerbation group. Higher levels of ferritin and KL‐6 and HRCT scores were independently associated with poor prognosis. The 1‐year survival rate was significantly lower in patients with high KL‐6 level than in those with low KL‐6 level. Conclusion The serum KL‐6 levels may be a useful marker for predicting and monitoring ILD in Chinese patients with anti‐MDA5+ DM, especially amyopathic DM phenotype.

Initial Predictors for Short-termprognosisin Anti-melanoma Differentiation-associated Protein-5 Positive Patients

“…Our study has revealed a high prevalence of ILD inanti-MDA5 positive patients, consistentwith previous studies in Europeans and Japanese [2,20]. The short-term mortality rate of anti-MDA5 positive patients was especially high within the rst 6-12 months [5,9,13]. Based on these ndings, we set to analyze the rst six months living situation and identify the predictive factors for death in anti-MDA5 positive patients.…”

“…On the contrary, GGO was a quitecommon pattern in the early stage.Similarly, in a prospective study, patients with GGO in all six lung elds at baselineall died of respiratory failure during follow-up [5]. Fujikiet al [22]also reported the prognosis of patients with right middle lung lobe GGO score≥2 was poor.Different from the wide consensus on the utility ofCT score, the effect o nitial KL-6 level was still controversial in different reports [9,11,13,[21][22][23]. In our cohort, we found the cut off value of initial KL-6>1600U/mlas an independent poor prognostic predictor and the cumulative six-months survival rate differed signi cantly.…”

“…In our cohort, we found the cut off value of initial KL-6>1600U/mlas an independent poor prognostic predictor and the cumulative six-months survival rate differed signi cantly. In addition,Ye et al [13]reported initial KL-6 of 792U/ml as the cut-off for discriminating between survivors and nonsurvivors in anti-MDA5 positive patients.Moreover,dynamic change of KL-6 level, like markedincrease of serum KL-6 during the rst four weeks, has also been reported as apoor prognosticpredictor inPM/DM patients [23]. We inferred that higher total GGO score and KL-6 level both indicated a more rapid progression of ILD and wider extent of lung involvement, resulting in respiratory failure in the early stage.…”

“…Of note, in the studycontaining all types of myositis, anti-MDA5 has such a strong association with poor prognosis, that it dominates the analysis and makes other potential poor prognostic factors even tendto be a protective factor [11]. While in the subgroup of anti-MDA5 positive patients, the reported risk factors varied in different reports, possibly due to small sample size [5,9,13].…”

Initial Predictors for Short-Term Prognosis in Anti-Melanoma Differentiation-Associated Protein-5 Positive Patients

“…Of note, in the study containing all types of myositis, anti-MDA5 has such a strong association with poor prognosis, that it dominates the analysis and makes other potential poor prognostic factors even tend to be a protective factor [11]. While in the subgroup of anti-MDA5 positive patients, the reported risk factors varied in different reports, possibly due to small sample size [5,9,13].…”