Summary: Study reveals mice with antibody-induced rheumatoid arthritis went on to develop spinal lesions similar to those associated with axial spondyloarthritis.
Source: University of Colorado Anschutz Medical Campus
Researchers at the University of Colorado Anschutz Medical Campus have discovered that having one kind of autoimmune disease can lead to another.
The scientists serendipitously found that mice with antibody-induced rheumatoid arthritis in their joints went on to develop spinal lesions similar to those in axial spondyloarthritis (AxSpA) which causes fusion of the vertebrate and curvature, or bending, of the backbone.
The study was published today in the journal Immune Network.
“Our results suggest that one autoimmune disease, such as inflammatory arthritis, may also lead to a secondary autoimmune disease such as AxSpA,” said the study’s lead author Nirmal Banda, Ph.D., professor in the division of rheumatology at the University of Colorado School of Medicine. “This interesting disease association may be due to the binding of anti-collagen autoantibodies to the spine, or to some alteration of the immune system that requires further investigation.”
These same anti-collagen antibodies are also present in humans with arthritis. They directly attack joint cartilage resulting in inflammation and pain.
Banda noted that every mouse injected with collagen antibody-induced arthritis (CAIA) developed arthritis and then curvature of the spine consistent with axial spondyloarthritis.
“I began to notice the proliferation of bone in the spine and fusing of the vertebrate,” he said. “The normal spaces between the spine vertebrate in certain location were disappearing. This is similar to what happens to humans with AxSpA.”
The connection, he said, has not been made in any other study he’s seen.
“I believe we are the first to make this link,” he said.
But exactly how one autoimmune disease could trigger another remains a mystery, one that Banda hopes to investigate.
“I want to know what the mechanism is,” he said.
In the meantime, he suggested that those with an autoimmune disease be vigilant in case they develop another.
“I believe because of our changing environment we are seeing a growth in autoimmune diseases,” he said. “There are already connections between gum disease and rheumatoid arthritis and dry age-related macular degeneration and rheumatoid arthritis. I believe this is an area that needs further exploration.”
A Potential New Mouse Model of Axial Spondyloarthritis Involving the Complement System
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.