Vimentin as antigenic target in autoimmunity: A comprehensive review

Area of Science:

• Immunology
• Cell Biology
• Protein Biochemistry

Background:

• Vimentin is an intermediate filament protein crucial for cellular physiology, interactions, and immune function.
• Native and post-translationally modified vimentin forms are implicated in the pathogenesis of various autoimmune and inflammatory diseases.
• Modifications create antigenic epitopes, leading to autoantibody synthesis.

Purpose of the Study:

• To review the role of vimentin and its modifications in the pathogenesis of autoimmune diseases.
• To highlight vimentin-derived autoantibodies as potential diagnostic and prognostic markers.
• To explore the specific involvement of vimentin in rheumatoid arthritis, sarcoidosis, lupus, antiphospholipid syndrome, Crohn's disease, and ankylosing spondylitis.

Main Methods:

• Literature review and synthesis of existing research on vimentin's role in autoimmune diseases.
• Analysis of specific vimentin modifications (citrullination, carbamylation, acetylation, MMP-degradation) and their antigenic properties.
• Examination of autoantibody targets and their clinical significance in various autoimmune conditions.

Main Results:

• Modified vimentin (citrullinated, carbamylated, acetylated) is central to rheumatoid arthritis pathogenesis, with corresponding antibodies as diagnostic markers.
• Native vimentin epitopes are antigenic in HLA-DRB1*0301 positive sarcoidosis patients.
• Vimentin contributes to lupus-related tubulointerstitial inflammation and glomerulonephritis.
• Vimentin-cardiolipin complexes on apoptotic cells drive antiphospholipid syndrome pathogenesis and thrombosis.
• Citrullinated and MMP-degraded vimentin are found in Crohn's disease and ankylosing spondylitis.

Conclusions:

• Vimentin and its post-translational modifications play a significant role in the pathogenesis of multiple autoimmune diseases.
• Vimentin-based autoantibodies represent promising diagnostic and prognostic biomarkers for these conditions.
• Targeting vimentin pathways may offer therapeutic strategies for autoimmune disorders.