Citrullinated vimentin (citVIM)

Citrullinated vimentin is a post-translationally modified form of the type III intermediate filament protein vimentin, generated when arginine residues are converted to citrulline by peptidylarginine deiminase (PAD) enzymes, particularly PAD2 and PAD4 [Vossenaar et al., 2004]. This modification changes the protein's overall charge and structural conformation, which can lead to the exposure of neoepitopes that are recognized as foreign by the immune system [Bang et al., 2007]. In the context of autoimmune diseases such as rheumatoid arthritis, citrullinated vimentin serves as a major autoantigen and a target for anti-citrullinated protein antibodies (ACPAs), contributing significantly to joint inflammation and damage [Mor-Vaknin et al., 2003]. In addition to its role in autoimmunity, citrullinated vimentin is expressed on the surface of several types of tumor cells, making it a promising target for cancer immunotherapy [Cook et al., 2018]. For example, the Modi-1 vaccine is designed to stimulate cytotoxic T-cell responses against citrullinated proteins, including vimentin, in solid tumors such as triple-negative breast cancer and ovarian cancer [Scallan et al., 2021]. Therapeutic development currently focuses on vaccines that target these neoantigens or small molecules that inhibit PAD enzymes to prevent the formation of citrullinated proteins in inflammatory contexts. Furthermore, antibodies against mutated citrullinated vimentin (MCV) are widely used as a high-specificity diagnostic biomarker for early rheumatoid arthritis [Innala et al., 2014].

Other names

Mutated citrullinated vimentinMCVcit-VIMCitrullinated-Vimentin

Induction of CD4+ T-cell-mediated immune responses against citrullinated neoepitopes expressed on the surface of tumor cells (Modi-1); inhibition of peptidylarginine deiminase (PAD) enzymes to prevent the post-translational modification of vimentin [Scallan et al., 2021] [Cuzic et al., 2017].