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A Potential New Mouse Model of Axial Spondyloarthritis Involving the Complement System

  • V. Michael Holers (Division of Rheumatology, School of Medicine, University of Colorado, Anschutz Medical Campus) ;
  • Francisco G. La Rosa (Department of Pathology, School of Medicine, University of Colorado, Anschutz Medical Campus) ;
  • Nirmal K. Banda (Division of Rheumatology, School of Medicine, University of Colorado, Anschutz Medical Campus)
  • Received : 2021.10.18
  • Accepted : 2021.12.04
  • Published : 2021.12.31
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Abstract

Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.

Keywords

Acknowledgement

Dr. Banda is grateful to faculty members and also an international scientists because after the discovery phase some or all of these data has been shared from time to time prior to publication for consultation with Dr. Robert I. Scheinman, PhD, University of Colorado Anschutz, Dr. Liron Kaplan, MD, PhD Denver Veterans Affairs Medical Center and Dr. Anne Troldborg, MD, PhD, Aarhus University Hospital, Denmark. The National Institutes of Health grant R01AR51749 to VMH (PI) and NKB (Co-I).

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