Homocitrullinated Aldolase A (HC-ALDOA)

Homocitrullinated Aldolase A is a post-translationally modified form of the glycolytic enzyme Fructose-bisphosphate aldolase A, where lysine residues are converted to homocitrulline through a non-enzymatic process called carbamylation (UniProt P04075; Verheul et al., 2016). This modification is driven by elevated levels of cyanate, which occurs during chronic inflammation, smoking, or uremia associated with chronic kidney disease. In Rheumatoid Arthritis (RA), homocitrullinated Aldolase A serves as a key autoantigen, leading to the production of anti-carbamylated protein (anti-CarP) antibodies, which are clinical biomarkers for disease severity and joint erosion (Shi et al., 2011). In the field of oncology, homocitrullinated proteins are recognized as stress-induced post-translational modifications (siPTMs) that can act as neoantigens. These neoantigens are being explored as targets for cancer immunotherapies, such as the Moditope platform (e.g., Modi-2), which aims to induce T-cell mediated destruction of tumor cells that present these modified peptides under metabolic stress (Scancell Holdings). Consequently, Homocitrullinated Aldolase A represents a dual-interest target for both the diagnosis of autoimmune disorders and the development of novel cancer vaccines.

Other names

Carbamylated Aldolase ACarbamylated Fructose-bisphosphate aldolase AHC-ALDOAHomocitrullinated ALDOA

Stimulation of CD4+ T-cell responses against homocitrullinated neoepitopes presented on MHC class II molecules.