Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome.

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients.

Remuzgo-Martínez S ，Atienza-Mateo B ，Ocejo-Vinyals JG ，Genre F ，Pulito-Cueto V ，Mora-Cuesta VM ，Iturbe-Fernández D ，Lera-Gómez L ，Pérez-Fernández R ，Prieto-Peña D ，Irure J ，Romero-Bueno F ，Sanchez-Pernaute O ，Alonso-Moralejo R ，Nuño L ，Bonilla G ，Vicente-Rabaneda EF ，Grafia I ，Prieto-González S ，Narvaez J ，Trallero-Araguas E ，Selva-O'Callaghan A ，Spanish Biomarkers of Antisynthetase Syndrome Consortium ，Spanish Biomarkers of Interstitial Lung Disease Consortium ，Gualillo O ，Cavagna L ，Cifrián JM ，Renzoni EA ，Castañeda S ，López-Mejías R ，González-Gay MA ... -  《Scientific Reports》

[Characteristics and clinical significance of pulmonary function test and KL-6 in ASSD-ILD and IPF].

Sun D ，Cheng Z ，Jiang TC ，Li PF ，Jia LQ ，Wang TT ，Zheng CP ，Li Y ，Duo MJ ... -  《-》

Influence of MUC5B gene on antisynthetase syndrome.

López-Mejías R ，Remuzgo-Martínez S ，Genre F ，Pulito-Cueto V ，Rozas SMF ，Llorca J ，Fernández DI ，Cuesta VMM ，Ortego-Centeno N ，Gómez NP ，Mera-Varela A ，Martínez-Barrio J ，López-Longo FJ ，Mijares V ，Lera-Gómez L ，Usetti MP ，Laporta R ，Pérez V ，Gafas AP ，González MAA ，Calvo-Alén J ，Romero-Bueno F ，Sanchez-Pernaute O ，Nuno L ，Bonilla G ，Balsa A ，Hernández-González F ，Grafia I ，Prieto-González S ，Narvaez J ，Trallero-Araguas E ，Selva-O'Callaghan A ，Gualillo O ，Castañeda S ，Cavagna L ，Cifrian JM ，González-Gay MA ... -  《Scientific Reports》

Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases.

Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. Because injury and/or regeneration of type II pneumocytes are prominent histological features of ILDs, substances derived from type II pneumocytes have been the focus of research investigating potential biomarkers for ILD. One important biomarker for ILD is the high-molecular-weight glycoprotein, Krebs von den Lungen-6 (KL-6). KL-6 is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with ILD. KL-6/MUC1 is detectable in the serum of patients with ILD, and extensive investigations performed primarily in Japan have revealed that serum KL-6/MUC1 is elevated in 70-100% of patients with various ILDs, including idiopathic interstitial pneumonias, collagen vascular disease-associated interstitial pneumonia, hypersensitivity pneumonia, radiation pneumonitis, drug-induced ILDs, acute respiratory distress syndrome, pulmonary sarcoidosis, and pulmonary alveolar proteinosis. The results from these various studies have supported the utility of KL-6/MUC1 as a serum biomarker for detecting these various ILDs. Moreover, KL-6/MUC1 serum levels have been demonstrated to be useful for evaluating disease activity and predicting the clinical outcomes of various ILD types. Based on these observations, we believe that KL-6/MUC1 is currently one of the best and most reliable serum biomarkers available for ILD management.

Ishikawa N ，Hattori N ，Yokoyama A ，Kohno N ... -  《-》

Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis.

Kennedy B ，Branagan P ，Moloney F ，Haroon M ，O'Connell OJ ，O'Connor TM ，O'Regan K ，Harney S ，Henry MT ... -  《-》