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

Abstract

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.

• Authors: Raja Atreya, Helmut Neumann, Clemens Neufert, Maximilian J Waldner, Ulrike Billmeier, Yurdagül Zopf, Marcus Willma, Christine App, Tino Münster, Hermann Kessler, Stefanie Maas, Bernd Gebhardt, Ralph Heimke-Brinck, Eva Reuter, Frank Dörje, Tilman T Rau, Wolfgang Uter, Thomas D Wang, Ralf Kiesslich, Michael Vieth, Ewald Hannappel, Markus F Neurath
• Journal: Nature medicine (Nat Med) Vol. 20 Issue 3 Pg. 313-8 (Mar 2014) ISSN: 1546-170X [Electronic] United States
• PMID: 24562382 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Fluorescent Dyes
• Immunoglobulin G
• Tumor Necrosis Factor-alpha
• Adalimumab

Topics

• Adalimumab
• Adult
• Antibodies, Monoclonal (chemistry)
• Antibodies, Monoclonal, Humanized (chemistry)
• Crohn Disease (metabolism, therapy)
• Endoscopy, Gastrointestinal
• Female
• Fluorescent Antibody Technique
• Fluorescent Dyes (chemistry)
• Humans
• Immunoglobulin G (chemistry)
• Immunotherapy (methods)
• Inflammation
• Intestinal Mucosa (metabolism, pathology)
• Intestines (pathology)
• Male
• Microscopy, Confocal
• Middle Aged
• Prospective Studies
• Treatment Outcome
• Tumor Necrosis Factor-alpha (chemistry)