IgA-Seq Analysis to Advance the Study of Host Immunity-Microbiome Interactions in Osteoarthritis
Abstract
Post-traumatic osteoarthritis (PTOA) is a chronic, debilitating musculoskeletal disease that disproportionately affects military personnel, resulting in pain, mobility loss, increased morbidity, and early mortality. PTOA is the most common form of arthritis among active-duty military personnel and the most common condition resulting in permanent disability in the military, and roughly 95% of PTOA cases have a history of prior combat injury. In fact, even with the best currently available treatment, the risk of PTOA following significant joint injury exceeds 50%. Soldiers are more than five times more likely to develop this form of arthritis than the general population, and these rates are accelerating over time; for example, the rate of PTOA doubled in the decade from 2005 to 2014. Despite the significant burden of PTOA in the military, we have no treatments to prevent or slow the development of PTOA. In fact, our therapeutic arsenal is limited to pain relief and eventual joint replacement. Previous studies have shown that PTOA is a disease of local and systemic inflammation, although the ways in which the immune system interacts with environmental factors to produce PTOA are unclear. One potential mechanism of environmental-immune interaction are microbiome effects. In this study, we will evaluate both the pathogenic and potential protective effects of changes in body microbiomes along with their interactions with the immune system in PTOA, using cutting-edge microbiome and immune cell subtyping analyses. We will use a well- established PTOA animal model, the disruption of medial meniscus (DMM) mouse model. We will compare the microbiome and immune cell responses to induction of osteoarthritis (OA) by DMM in both wild-type mice and mice protected from PTOA (the MRL/MpJ mouse) and evaluate how the immune system interacts with the microbiome in each of these conditions. Success in our study would lead not only to a new understanding of the ways in which environmental factors affect susceptibility to PTOA, but also to potential paradigm-shifting treatments for PTOA, which would be both accessible and readily deployable in the battlefield.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310101
Entities
People
- Matlock Jeffries
Organizations
- Oklahoma Medical Research Foundation
- United States Army