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

Rheumatology (Oxford). 2018 Apr 1;57(4):737-747. doi: 10.1093/rheumatology/kex456.

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 anti-fibroblast 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / diagnostic imaging*
  • Arthritis / drug therapy
  • Arthritis / genetics
  • Cartilage, Articular / diagnostic imaging*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Collagen / toxicity
  • Disease Models, Animal
  • Gelatinases / biosynthesis
  • Gelatinases / genetics*
  • Gene Expression Regulation*
  • Immunohistochemistry
  • Interleukins / biosynthesis
  • Interleukins / genetics*
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred DBA
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / genetics*
  • Single Photon Emission Computed Tomography Computed Tomography / methods*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology

Substances

  • Interleukins
  • Membrane Proteins
  • RNA, Messenger
  • Collagen
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases
  • interleukin-22