Anti-UBE2T antibody: A novel biomarker of progressive-fibrosing interstitial lung disease

被引:1
作者
Ujike-Hikichi, Mari [1 ]
Gon, Yasuhiro [1 ]
Ooki, Takashi [1 ]
Morisawa, Tomoko [1 ]
Mizumura, Kenji [1 ]
Kozu, Yutaka [1 ]
Hiranuma, Hisato [1 ]
Nakagawa, Yoshiko [1 ]
Shimizu, Tetsuo [1 ]
Maruoka, Shuichiro [1 ,2 ]
机构
[1] Nihon Univ, Dept Internal Med, Div Resp Med, Sch Med, Tokyo, Japan
[2] Nihon Univ, Dept Internal Med, Div Resp Med, Sch Med, Oyaguchikamimachi 30-1,Itabashi Ku, Tokyo 1738610, Japan
关键词
Progressive fibrosing interstitial; lung disease; Pulmonary fibrosis; Autoantibody; Ubiquitin-conjugating enzyme E2T; IDIOPATHIC PULMONARY-FIBROSIS; CLINICAL-SIGNIFICANCE; RHEUMATOLOGY/EUROPEAN LEAGUE; CLASSIFICATION CRITERIA; CELL-PROLIFERATION; AMERICAN-COLLEGE; UBE2T; AUTOANTIBODIES; EXPRESSION; ACCUMULATE;
D O I
10.1016/j.resinv.2023.05.006
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: Anti-fibrotic therapy has demonstrated efficacy against progressive-fibrosing interstitial lung disease (PF-ILD); therefore, identifying disease behavior before progression has become a priority. As autoimmunity is implicated in the pathogenesis of various ILDs, this study explored circulating biomarkers that could predict the chronic progressive behavior of ILDs.Methods: A single-center retrospective cohort study was conducted. Circulating autoantibodies in patients with ILD were screened using microarray analysis to identify candidate biomarkers. An enzyme-linked immunosorbent assay was performed with a larger sample set for the quantification of antibodies. After 2 years of follow-up, ILDs were reclassified as PF or non-PF. The relationship between the participants' autoantibody levels measured at enrolment and final diagnosis of PF-ILD was determined.Results: In total, 61 healthy participants and 66 patients with ILDs were enrolled. Antiubiquitin-conjugating enzyme E2T (UBE2T) antibody was detected as a candidate biomarker. Anti-UBE2T antibody levels were elevated in patients with idiopathic pulmonary fibrosis (IPF). After following up on the study participants for 2 years, anti-UBE2T levels measured at enrolment significantly correlated with the new PF-ILD diagnosis. Immunohistochemical staining of normal lung tissues revealed sparsely located UBE2T in the bronchiole epithelium and macrophages, whereas IPF lung tissues showed robust expression in the epithelial lining of honeycomb structures.Conclusion: To our knowledge, this is the first report to describe an anti-UBE2T antibody, a new biomarker that is significantly elevated in patients with ILD who present future disease progression.
引用
收藏
页码:579 / 587
页数:9
相关论文
共 33 条
[11]   Clinical Significance of Serum Autoantibodies in Idiopathic Interstitial Pneumonia [J].
Kang, Bo Hyoung ;
Park, Jin Kyeong ;
Roh, Jae Hyung ;
Song, Jin Woo ;
Lee, Chang Keun ;
Kim, Miyoung ;
Jang, Se Jin ;
Colby, Thomas V. ;
Kim, Dong Soon .
JOURNAL OF KOREAN MEDICAL SCIENCE, 2013, 28 (05) :731-737
[12]   Idiopathic nonspecific interstitial pneumonia - Lung manifestation of undifferentiated connective tissue disease? [J].
Kinder, Brent W. ;
Collard, Harold R. ;
Koth, Laura ;
Daikh, David I. ;
Wolters, Paul J. ;
Elicker, Brett ;
Jones, Kirk D. ;
King, Talmadge E., Jr. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 176 (07) :691-697
[13]   Global Impairment of CD4+CD25+FOXP3+ Regulatory T Cells in Idiopathic Pulmonary Fibrosis [J].
Kotsianidis, Ioannis ;
Nakou, Evangelia ;
Bouchliou, Irene ;
Tzouvelekis, Argyrios ;
Spanoudakis, Emmanouil ;
Steiropoulos, Paschalis ;
Sotiriou, Ioannis ;
Aidinis, Vassilis ;
Margaritis, Dimitrios ;
Tsatalas, Costas ;
Bouros, Demosthenes .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2009, 179 (12) :1121-1130
[14]   Prevalence and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis [J].
Lee, Joyce S. ;
Kim, Eunice J. ;
Lynch, Kara L. ;
Elicker, Brett ;
Ryerson, Christopher J. ;
Katsumoto, Tamiko R. ;
Shum, Anthony K. ;
Wolters, Paul J. ;
Cerri, Stefania ;
Richeldi, Luca ;
Jones, Kirk D. ;
King, Talmadge E., Jr. ;
Collard, Harold R. .
RESPIRATORY MEDICINE, 2013, 107 (02) :249-255
[15]  
Liu JC, 2017, INT J CLIN EXP PATHO, V10, P9482
[16]   UBE2T knockdown inhibits gastric cancer progression [J].
Luo, Changjiang ;
Yao, Yunyi ;
Yu, Zeyuan ;
Zhou, Huinian ;
Guo, Lingyun ;
Zhang, Junqiang ;
Cao, Hongtai ;
Zhang, Genyuan ;
Li, Yumin ;
Jiao, Zuoyi .
ONCOTARGET, 2017, 8 (20) :32639-32654
[17]   UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation [J].
Machida, Yuichi J. ;
Machida, Yuka ;
Chen, Yuefeng ;
Gurtan, Allan M. ;
Kupfer, Gary M. ;
D'Andrea, Alan D. ;
Dutta, Anindya .
MOLECULAR CELL, 2006, 23 (04) :589-596
[18]   Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial [J].
Maher, Toby M. ;
Corte, Tamera J. ;
Fischer, Aryeh ;
Kreuter, Michael ;
Lederer, David J. ;
Molina-Molina, Maria ;
Axmann, Judit ;
Kirchgaessler, Klaus-Uwe ;
Samara, Katerina ;
Gilberg, Frank ;
Cottin, Vincent .
LANCET RESPIRATORY MEDICINE, 2020, 8 (02) :147-157
[19]   Dendritic cells accumulate in human fibrotic interstitial lung disease [J].
Marchal-Somme, Joeelle ;
Uzunhan, Yurdagul ;
Marchand-Adam, Sylvain ;
Kambouchner, Marianne ;
Valeyre, Dominique ;
Crestani, Bruno ;
Soler, Paul .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 176 (10) :1007-1014
[20]   Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study) [J].
Nasser, Mouhamad ;
Larrieu, Sophie ;
Si-Mohamed, Salim ;
Ahmad, Kais ;
Boussel, Loic ;
Brevet, Marie ;
Chalabreysse, Lara ;
Fabre, Celine ;
Marque, Sebastien ;
Revel, Didier ;
Thivolet-Bejui, Francoise ;
Traclet, Julie ;
Zeghmar, Sabrina ;
Maucort-Boulch, Delphine ;
Cottin, Vincent .
EUROPEAN RESPIRATORY JOURNAL, 2021, 57 (02)