Metabolic-epigenetic rewiring in rheumatoid arthritis: from pathogenic memory to precision restoration

Under specific environmental and nutritional conditions, the human body can restore normal physiological function in chronic autoimmune conditions through its inherent regenerative processes.

Autoantibodies that recognize chemically modified proteins in rheumatoid arthritis directly trigger immune complement activation and increase bone-destroying cell activity, leading to joint damage.

In rheumatoid synovial cells, increased levels of acetyl-CoA lead to chemical modifications on histones and RNA that increase the production of proteins involved in inflammation, resulting in persistent joint tissue damage and activation of immune cells.

In people with rheumatoid arthritis, an altered gut microbiome is associated with lower levels of short-chain fatty acids in the bloodstream, which results in altered epigenetic control of T cell development and a shift toward inflammatory T cell populations.

In rheumatoid arthritis, high levels of lactate in the joint fluid cause chemical changes to proteins in immune and joint cells, making them remain inflamed and resistant to cell death, which leads to ongoing joint damage and flare-ups even when patients receive immune-suppressing treatments.

In inflamed joints affected by rheumatoid arthritis, low levels of NAD+ reduce the activity of Sirtuin enzymes, leading to excessive protein acetylation that sustains inflammation and impairs energy production in immune and joint cells.