The Clinical Significance of Tumor-associated Antigens in Dermatomyositis Patients with Interstitial Lung Disease

YANG Yuan, HAO Jing-cheng, CHEN Yuan. et al

Abstract

To investigate the relationship between tumor related markers and the presence of interstitial lung disease (ILD) in dermatomyositis (DM) patients as well as potential serum markers for accompanied ILD. MethodsFifty-nine DM patients were included, including 30 patents with ILD. Serum level of anti-transcription intermediary factor1-γ (TIF1-γ) and tumor-associated antigens (TAAs) were detected to analyze the correlation of these markers with ILD. Meanwhile, the diagnostic value of these markers was evaluated by receive operating characteristic (ROC) curve analysis. ResultsWe found that there were 5 patients bearing malignancies, independent from the presence of ILD (P=0.024). Serum anti-TIF1-γ was positive in 4/5 DM patients with tumor, of which sensitivity and specificity were 36.36% and 97.92%, respectively. In contrast, only one case was found positive anti-TIF1-γ in 30 DM with ILD (P=0.002). carbohydrate antigen (CA)125, CA153, and cytokeratin-19 fragment (CYFRA21-1) were elevated in DM patients with ILD in compared to those without ILD. The area under curve (AUC) of CYFRA21-1 for the prediction of ILD was 0.745 (P=0.002). The optimal cut-off value was 3.58 ng/mL with a sensitivity of 60.71% and a specificity of 84.00%. The AUC in combination of CA125 and CYFRA21-1 could reach 0.801 (P<0.002) with a sensitivity of 64.29% and a specificity of 82.61%. ConclusionPresence of malignance and positive anti-TIF1γ could be the protective factors for ILD in DM. Elevated serum levels of CA125, CA153, CYFRA21-1 could indicate the accompanying ILD.

 

Keywords: DermatomyositisInterstitial lung disease, Transcription intermediary factor 1-γ, Tumor-associated antigens 

 

Full Text:

PDF


References


YAMASAKI Y, YAMADA H, OHKUBO M, et al. Long-term survival and associated risk factors in patients with adult-onset idiopathic inflammatory myopathies and amyopathic dermatomyositis: experience in a single institute in Japan. J Rheumatol.2011,38(8); 1636-1643.

COTTIN V, THIVOLET-BEJUI F. REYNAUD- GAUBERT M. et al. Interstitial lung disease in amyopathic dermatomyositis, dermatomyositis and polymyositis. Eur Respir J ,2003,22(2):245-250.

FUJISAWA T, SUDA T. NAKAMURA Y, et al. Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis. J Rheumatol.2005,32( 1):58-64.

VALERIO-MARZANO A, MORABITO A, BERTI E, et al. Elevated circulating С A 15. 3 levels in a subset of systemic sclerosis with severe lung involvement. Arch Dermatol. 1998,134 (5): 645.

KIM HR. LEE CH, KIM YW. et al. Increased CA 19-9 level in patients without malignant disease. Clin Chem Lab Med,2009,47(6);750-754.

MEDRANDA GOMEZ MA, PARICIO NUNEZ P, TOVAR MARTINEZ A, et al. CA 199 and pulmonary fibrosis. Rev Esp Enferm Dig,2005,97( 11):843-844.

SZEKANECZ E, SAN DOR Z, ANTAL-SZALMAS Wetal. Increased production of the soluble tumor-associated antigens CA19-9, CA125 and CA15-3 in rheumatoid arthritis; potential adhesion molecules in synovial inflammation? Ann N Y Acad Sci,2007,1108:359-371.

SZEKANECZ E, ANDRAS C, SANDOR Z, et al. Malignancies and soluble tumor antigens in rheumatic disease. Autoimmun Rev,2006,6( 1):42-47.

BOHAN A, PETER JB. Polymyositis and dematomyositis (first of two parts). N Engl J Med, 1975,292(7) :344-347. BOHAN A, PETER JB. Polymyositis and dematomyositis (first of two parts). N Engl J Med, 1975,292(8) :403-407.

American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society ( ATS), and the European Respiratory Society ( ERS ) was adopted by the ERS Executive Committee, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med, 2002, 165(2):277-304.

KAMEDAH, TAKEUCHI T. Recent advances in the treatment of interstitial lung disease in patients with polymyositis/ dermatomyositis. Endocr Metab Immune Disord Drug Targets,2006 ,6(4) s409-415.

TARGOFF IN, MAMYROVA G, TRIEU EP, et al. A novel autoantibody to a 155-kI) protein is associated with dermatomyositis. Arthritis Rheum,2006 ,54(11): 3682-3689.

TRALLERO ARAGUAS E, RODRIGO PENDAS JA, SELVA- O’CALLAGHAN A, et al. Usefulness of anti-pl55 autoantibody for diagnosing cancer-associated dermatomyositis: a systematic review and meta-analysis. Arthritis Rheum,2012,64(2) ;523-532.

FUJIMOTOM, HAMAGUCHI Y, KAJI K, et al. Myositis-specific anti-155/140 autoantibodies target transcriptional intermediary factor 1 family proteins. Arthritis Rheum,2012,64(2) ;513-522.

HOSHINO K. MURO Y, SUGIURA K, et al. Anti-MDA5 and anti-TIFl-gamma antibodies have clinical significance for patients with dermatomyositis. Rheumatology ( Oxford ), 2010,49(9):1726-1733.

TRALLERO ARAGUAS E, LABRADOR HORRILLO M, SELVA-O, CALLAGHAN A, et al. Cancer-associated myositis and anti-pl55 autoantibody in a series of 85 patients with idiopathic inflammatory myopathy. Medicine (Baltimore) ,2010,89( 1) :47-52.

SZEKANECZ E. SZUCSG, SZEKANECZ Z. et al. Tumor associated antigens in systemic sclerosis and systemic lupus erythematosus; associations with organ manifestations, immunolaboratory markers and disease activity indices. J Autoimmun,2008.31(4):372-376.

BALDUSSE, ENGELMANN K. HANISH FG. MUC1 and the MUCsta family of human mucins with impact in cancer biology. Crit Rev Clin Lab Sci,2004 ,41(2); 189-231.

NAKAYAMA М» SATOH H, ISHIKAWA H, et al. Cytokeratin 19 fragment in patients with nonmalignant respiratory diseases. Chest,2003,123(6) ;2001-2006.

INAGE M. NAKAMURA H, KATO S, et al. Levels of cytokeratin 19 fragments in hronchoalveolar lavage fluid correlate to the intensity of neutrophil and eosinophilalveolitis in patients with idiopathic pulmonary fibrosis. Respir Med, 2000,94(2):155-160.

INGE M. VERCAUTERE N, STIJN E, et al. CYFRA 21.1 in hronchoalveolar las'age of idiopathic pulmonary fibrosis patients. Exp Lung Res,2015,41(8):459-465.

NAKAMURA H. ABE S, SHI BATA Y. et al. Elevated levels of cytokeratin 19 in the hronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases a specific marker for bronchial epithelial injury. Am J Respir Crit Care Med, 1997,155(4): 1217-1221.


Refbacks

  • There are currently no refbacks.