Homocitrullinated fructose-bisphosphate aldolase A (Homocit-ALDOA)

Homocitrullinated fructose-bisphosphate aldolase A is a post-translationally modified form of the glycolytic enzyme aldolase A, where lysine residues are converted to homocitrulline through a non-enzymatic process called carbamylation (Trouw et al., 2017, Nature Reviews Rheumatology). This modification is often triggered by elevated levels of cyanate, which can occur during chronic inflammation, smoking, or renal impairment (Shi et al., 2011, PNAS). In patients with rheumatoid arthritis (RA), homocitrullinated aldolase A acts as a neoantigen, triggering an autoimmune response and the production of anti-carbamylated protein (anti-CarP) antibodies (Verheul et al., 2016, Annals of the Rheumatic Diseases). These anti-CarP antibodies are significant clinical biomarkers, often predating the onset of clinical symptoms and correlating with more severe joint destruction and disease progression (Shi et al., 2011, PNAS). While native aldolase A normally functions in the glycolytic pathway to catalyze the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, its homocitrullinated form is primarily studied for its role in breaking immune tolerance. Current therapeutic approaches do not target the protein directly with small molecules but focus on modulating the broader immune response using agents like Rituximab or exploring antigen-specific tolerogenic vaccines to suppress the specific B and T cell activity directed against such neoantigens (Trouw et al., 2017, Nature Reviews Rheumatology).

Other names

Carbamylated aldolase AHomocitrullinated ALDOACarbamylated fructose-bisphosphate aldolase AHomocitrullinated aldolase

Modulation of the autoimmune response against neoantigens through B-cell depletion, T-cell costimulation blockade, or systemic anti-inflammatory signaling.