In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease

被引：307

作者：

Atreya, Raja ^{[1
]}

Neumann, Helmut ^{[1
]}

Neufert, Clemens ^{[1
]}

Waldner, Maximilian J. ^{[1
]}

Billmeier, Ulrike ^{[1
]}

Zopf, Yurdaguel ^{[1
]}

Willma, Marcus ^{[1
]}

App, Christine ^{[2
]}

Muenster, Tino ^{[3
]}

Kessler, Hermann ^{[4
]}

Maas, Stefanie ^{[5
]}

Gebhardt, Bernd ^{[5
]}

Heimke-Brinck, Ralph ^{[6
]}

Reuter, Eva ^{[6
]}

Doerje, Frank ^{[6
]}

Rau, Tilman T. ^{[7
]}

Uter, Wolfgang ^{[8
]}

Wang, Thomas D. ^{[9
]}

Kiesslich, Ralf ^{[10
]}

Vieth, Michael ^{[11
]}

Hannappel, Ewald ^{[2
]}

Neurath, Markus F. ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Med Clin 1, D-91054 Erlangen, Germany

[2] Univ Erlangen Nurnberg, Dept Biochem, D-91054 Erlangen, Germany

[3] Univ Erlangen Nurnberg, Dept Anesthesiol, D-91054 Erlangen, Germany

[4] Univ Erlangen Nurnberg, Dept Surg, D-91054 Erlangen, Germany

[5] Univ Erlangen Nurnberg, Ctr Clin Studies, D-91054 Erlangen, Germany

[6] Univ Erlangen Nurnberg, Erlangen Univ Hosp, Dept Pharm, D-91054 Erlangen, Germany

[7] Univ Erlangen Nurnberg, Dept Pathol, D-91054 Erlangen, Germany

[8] Univ Erlangen Nurnberg, Dept Med Informat Biometry & Epidemiol, D-91054 Erlangen, Germany

[9] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA

[10] St Marys Hosp, Med Clin, Frankfurt, Germany

[11] Klinikum Bayreuth, Inst Pathol, Bayreuth, Germany

来源：

NATURE MEDICINE | 2014年 / 20卷 / 03期

关键词：

INFLAMMATORY BOWEL DISEASES; PROPRIA T-LYMPHOCYTES; INFLIXIMAB; APOPTOSIS; ENDOSCOPY; DYSPLASIA; CANCER; ENDOMICROSCOPY; IDENTIFICATION; CHEMOTHERAPY;

D O I：

10.1038/nm.3462

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohn's disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohn's disease led to detection of intestinal mTNF(+) immune cells during confocal laser endomicroscopy. Patients with high numbers of mTNF(+) cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF(+) cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohn's disease and autoimmune or inflammatory disorders.

引用

页码：313 / 318

页数：6

共 37 条

[1]

Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation:: Evidence in Crohn disease and experimental colitis in vivo [J].

Atreya, R ;

Mudter, J ;

Finotto, S ;

Müllberg, J ;

Jostock, T ;

Wirtz, S ;

Schütz, M ;

Bartsch, B ;

Holtmann, M ;

Becker, C ;

Strand, D ;

Czaja, J ;

Schlaak, JF ;

Lehr, HA ;

Autschbach, F ;

Schürmann, G ;

Nishimoto, N ;

Yoshizaki, K ;

Ito, H ;

Kishimoto, T ;

Galle, PR ;

Rose-John, S ;

Neurath, MF .

NATURE MEDICINE, 2000, 6 (05) :583-588

[2]

Antibodies Against Tumor Necrosis Factor (TNF) Induce T-Cell Apoptosis in Patients With Inflammatory Bowel Diseases via TNF Receptor 2 and Intestinal CD14+ Macrophages [J].

Atreya, Raja ;

Zimmer, Michael ;

Bartsch, Brigitte ;

Waldner, Maximilian J. ;

Atreya, Imke ;

Neumann, Helmut ;

Hildner, Kai ;

Hoffman, Arthur ;

Kiesslich, Ralf ;

Rink, Andreas D. ;

Rau, Tilman T. ;

Rose-John, Stefan ;

Kessler, Hermann ;

Schmidt, Jan ;

Neurath, Markus F. .

GASTROENTEROLOGY, 2011, 141 (06) :2026-2038

[3]

Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus [J].

Bird-Lieberman, Elizabeth L. ;

Neves, Andre A. ;

Lao-Sirieix, Pierre ;

O'Donovan, Maria ;

Novelli, Marco ;

Lovat, Laurence B. ;

Eng, William S. ;

Mahal, Lara K. ;

Brindle, Kevin M. ;

Fitzgerald, Rebecca C. .

NATURE MEDICINE, 2012, 18 (02) :315-321

[4]

Broadbridge VT, 2012, EXPERT REV ANTICANC, V12, P555, DOI [10.1586/era.12.25, 10.1586/ERA.12.25]

[5]

Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease. [J].

Colombel, Jean Frederic ;

Sandborn, William J. ;

Reinisch, Walter ;

Mantzaris, Gerassimos J. ;

Kornbluth, Asher ;

Rachmilewitz, Daniel ;

Lichtiger, Simon ;

D'Haens, Geert ;

Diamond, Robert H. ;

Broussard, Delma L. ;

Tang, Kezhen L. ;

van der Woude, C. Janneke ;

Rutgeerts, Paul .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (15) :1383-1395

[6]

Adalimumab Safety in Global Clinical Trials of Patients with Crohn's Disease [J].

Colombel, Jean-Frederic ;

Sandborn, William J. ;

Panaccione, Remo ;

Robinson, Anne M. ;

Lau, Winnie ;

Li, Ju ;

Cardoso, Alexandra T. .

INFLAMMATORY BOWEL DISEASES, 2009, 15 (09) :1308-1319

[7]

New therapies for inflammatory bowel disease: from the bench to the bedside [J].

Danese, Silvio .

GUT, 2012, 61 (06) :918-932

[8]

A review and expert opinion of the use of certolizumab for Crohn's disease [J].

Evans, Ashley T. ;

Lee, Scott D. .

EXPERT OPINION ON BIOLOGICAL THERAPY, 2012, 12 (03) :363-370

[9]

Identifying intestinal metaplasia at the squamocolumnar junction by using optical coherence tomography [J].

Evans, John A. ;

Bouma, Brett E. ;

Bressner, Jason ;

Shishkov, Milen ;

Lauwers, Gregory Y. ;

Mino-Kenudson, Mari ;

Nishioka, Norman S. ;

Tearney, Guillermo J. .

GASTROINTESTINAL ENDOSCOPY, 2007, 65 (01) :50-56

[10]

Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy [J].

Foersch, Sebastian ;

Kiesslich, Ralf ;

Waldner, Maximillian J. ;

Delaney, Peter ;

Galle, Peter R. ;

Neurath, Markus F. ;

Goetz, Martin .

GUT, 2010, 59 (08) :1046-1055

← 1 2 3 4 →