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 language | English |
|---|---|
| Pages (from-to) | 737-747 |
| Number of pages | 11 |
| Journal | Rheumatology (United Kingdom) |
| Volume | 57 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 18 Jan 2018 |
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Keywords
- UT-Hybrid-D
- Anti-IL-22
- Experimental arthritis
- SPECT/CT
- Therapy monitoring
- Anti-FAP
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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 journal › Article › Academic › peer-review
TY - JOUR
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
PY - 2018/1/18
Y1 - 2018/1/18
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.
KW - UT-Hybrid-D
KW - Anti-IL-22
KW - Experimental arthritis
KW - SPECT/CT
KW - Therapy monitoring
KW - Anti-FAP
UR - http://www.scopus.com/inward/record.url?scp=85045035254&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/kex456
DO - 10.1093/rheumatology/kex456
M3 - Article
VL - 57
SP - 737
EP - 747
JO - Rheumatology
JF - Rheumatology
SN - 1462-0324
IS - 4
ER -