# Impact of Immune Activation on Cardiovascular and Immune Health in RA

> **NIH VA I01** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2022 · —

## Abstract

Untreated rheumatoid arthritis (RA) carries high morbidity, including musculoskeletal disability and
cardiovascular disease. Fortunately, in the past 15 years we have been able to control rheumatoid arthritis very
well by offering methotrexate alone, leflunomide alone, TNF blocker therapy, rituximab, or a combination of
methotrexate and a biologic (genetically-engineered proteins derived from human genes) therapy. At the same
time, it is known that biologic agents contribute to an increased incidence of serious infections, impaired host
response to vaccines, and a modest increase in risk for cancer. For certain, these agents block both
pathogenic autoimmune disease activity pathways as well as the beneficial host response and host defense
pathways. Furthermore, rheumatoid arthritis itself is associated with increased systemic immune activation and
risk for cardiovascular disease. Our data, and that of others, indicate that chronic immune activation likely
contributes to immune dysfunction, as measured by host response to neo-antigen and recall antigen
immunization, and that immune activation predicts cardiovascular disease in the setting of chronic infection.
We propose here to investigate determinants of immune health in the setting of auto immune disease by
testing the hypothesis that in rheumatoid arthritis chronic immune activation (elevated sCD14, sCD163,
TNFR2, TNF, autotaxin, and CD8/DC/monocyte activation) predicts immune dysfunction, as manifest by
impaired host response to vaccine, and cardiac disease. This relationship is interrupted by TNF blockade. Aim
1: Determine whether immune activation, as reflected by elevated levels of sCD14, sCD163, autotaxin,
TNFR2, IL6, CRP, dendritic cell activation and monocyte activation, predict immune health, as
measured by host response to neo-antigen and recall antigen vaccine in treated RA, and whether TNF
blocking treatment modifies this relationship. Aim 2: Determine the relation between immune
activation, endothelial function, coronary atherosclerosis in RA, and whether TNF blockade improves
both immune activation and cardiovascular surrogates.

## Key facts

- **NIH application ID:** 10417005
- **Project number:** 5I01CX001791-03
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Donald D Anthony
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417005

## Citation

> US National Institutes of Health, RePORTER application 10417005, Impact of Immune Activation on Cardiovascular and Immune Health in RA (5I01CX001791-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10417005. Licensed CC0.

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