# Elucidating the Mechanisms that link the Shared Epitope, Periodontal Disease and Arthritis

> **NIH VA I01** · MEMPHIS VA MEDICAL CENTER · 2020 · —

## Abstract

Periodontal disease (PD) and Rheumatoid Arthritis (RA) have many features in common. PD is a chronic
inflammatory disease of the periodontium, the soft and hard tissues supporting the teeth, and is
characterized by the destruction of the alveolar bone as a result of the chronic bacterial challenge and a
compromised immune response. RA is a chronic inflammatory disease of the diarthrodial joints which
results in reduced mobility. Both diseases exhibit a strong genetic component, the “shared epitope” (SE)
HLA-DRβ1 as well as a lifestyle component such as tobacco use, a lifestyle choice that is prevalent
among veterans. We have previously demonstrated that when the shared epitope is added as a transgene
to a mouse that is known not to be susceptible to collagen-induced arthritis (CIA), this mouse (B10.M)
becomes susceptible to CIA. C57BL/6 (B6) mice have been described as not being susceptible to bone
loss or oral colonization with the putative PD pathogen, the gram negative anaerobe Porphyromonas
gingivalis in studies of PD. We have engineered a B6 mouse to express a chimeric mouse/human SE as a
transgene in the absence of its murine class II (B6.DR1 mouse), and we have begun studies to determine
if expression of this HLA-DRβ1 transgene can provide the B6 mouse with the appropriate set of
susceptibility genes necessary for colonization with P. gingivalis and for all the pathways that lead to bone
destruction.
The overarching goal of this program of study is to directly address the mechanistic basis behind the
association between periodontitis and the development of arthritis. We hypothesize that periodontitis in
the context of permissive tissue types (such as those bearing the SE) will provide the necessary pPAD
enzymes to promote host protein citrulline modifications that drive T cell development and subsequent
ACPA production. We further hypothesize that ACPAs form immune complexes that enhance vascular
permeability and allow binding of any number of joint specific antibodies to the cartilage where innate
mechanisms such as complement and FcR binding to propagate arthritis.
This study is significant because it has very important implications for veterans bearing the shared
epitope. Should our hypothesis prove correct, it will suggest that aggressive preventative measures
including a more pro-active periodontal screening with an enhanced frequency of visits may be necessary
to prevent arthritis in veterans bearing any allelic variation of the shared epitope. This might also include
arthritis that develops following acute injury to the joint.
Our preliminary data demonstrate 1) that we can establish an Pg oral infection model in the humanized
B6.DR1 mice and that the bacteria are present for a prolong period in the oral cavity, and can be
detected in the blood stream, 2) that infection of the oral cavity induces an immune response that can be
detected by the presence of ACPA, the generation of Th17 cells, and the induction of several
proinflammatory cyto...

## Key facts

- **NIH application ID:** 9898304
- **Project number:** 5I01BX003487-04
- **Recipient organization:** MEMPHIS VA MEDICAL CENTER
- **Principal Investigator:** DAVID D. BRAND
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898304

## Citation

> US National Institutes of Health, RePORTER application 9898304, Elucidating the Mechanisms that link the Shared Epitope, Periodontal Disease and Arthritis (5I01BX003487-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898304. Licensed CC0.

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