Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis

Tessa van der Geest, Debbie M. Roeleveld, Birgitte Walgreen, Monique M. Helsen, Tapan K. Nayak, Christian Klein, Martin Hegen, Gert Storm, Josbert M. Metselaar, Wim B. van den Berg, Peter M. van der Kraan, Peter Laverman, Otto C. Boerman, Marije I. Koenders (Corresponding Author)

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2 Citations (Scopus)

Abstract

Objectives. RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled antifibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis. Methods. Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores. Results. Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50%, vs 100% in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented. Conclusion. These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.

Original languageEnglish
Pages (from-to)737-747
Number of pages11
JournalRheumatology (United Kingdom)
Volume57
Issue number4
DOIs
Publication statusPublished - 18 Jan 2018

Fingerprint

Experimental Arthritis
Therapeutic Uses
Fibroblasts
Proteins
Arthritis
Antibodies
Joints
Pathology
Cytokines
Control Groups
Therapeutics
interleukin-22
Single-Photon Emission-Computed Tomography
Autoimmune Diseases
Cartilage
Chronic Disease
Bone and Bones
Injections
Incidence
Single Photon Emission Computed Tomography Computed Tomography

Keywords

  • UT-Hybrid-D
  • Anti-IL-22
  • Experimental arthritis
  • SPECT/CT
  • Therapy monitoring
  • Anti-FAP

Cite this

van der Geest, T., Roeleveld, D. M., Walgreen, B., Helsen, M. M., Nayak, T. K., Klein, C., ... Koenders, M. I. (2018). Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis. Rheumatology (United Kingdom), 57(4), 737-747. https://doi.org/10.1093/rheumatology/kex456
van der Geest, Tessa ; Roeleveld, Debbie M. ; Walgreen, Birgitte ; Helsen, Monique M. ; Nayak, Tapan K. ; Klein, Christian ; Hegen, Martin ; Storm, Gert ; Metselaar, Josbert M. ; van den Berg, Wim B. ; van der Kraan, Peter M. ; Laverman, Peter ; Boerman, Otto C. ; Koenders, Marije I. / Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis. In: Rheumatology (United Kingdom). 2018 ; Vol. 57, No. 4. pp. 737-747.
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abstract = "Objectives. RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled antifibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis. Methods. Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores. Results. Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50{\%}, vs 100{\%} in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented. Conclusion. These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.",
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van der Geest, T, Roeleveld, DM, Walgreen, B, Helsen, MM, Nayak, TK, Klein, C, Hegen, M, Storm, G, Metselaar, JM, van den Berg, WB, van der Kraan, PM, Laverman, P, Boerman, OC & Koenders, MI 2018, 'Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis' Rheumatology (United Kingdom), vol. 57, no. 4, pp. 737-747. https://doi.org/10.1093/rheumatology/kex456

Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis. / van der Geest, Tessa; Roeleveld, Debbie M.; Walgreen, Birgitte; Helsen, Monique M.; Nayak, Tapan K.; Klein, Christian; Hegen, Martin; Storm, Gert; Metselaar, Josbert M.; van den Berg, Wim B.; van der Kraan, Peter M.; Laverman, Peter; Boerman, Otto C.; Koenders, Marije I. (Corresponding Author).

In: Rheumatology (United Kingdom), Vol. 57, No. 4, 18.01.2018, p. 737-747.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis

AU - van der Geest, Tessa

AU - Roeleveld, Debbie M.

AU - Walgreen, Birgitte

AU - Helsen, Monique M.

AU - Nayak, Tapan K.

AU - Klein, Christian

AU - Hegen, Martin

AU - Storm, Gert

AU - Metselaar, Josbert M.

AU - van den Berg, Wim B.

AU - van der Kraan, Peter M.

AU - Laverman, Peter

AU - Boerman, Otto C.

AU - Koenders, Marije I.

N1 - OUP deal

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N2 - Objectives. RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled antifibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis. Methods. Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores. Results. Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50%, vs 100% in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented. Conclusion. These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.

AB - Objectives. RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled antifibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis. Methods. Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores. Results. Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50%, vs 100% in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented. Conclusion. These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.

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