Autoimmunity in rheumatoid arthritis: different antigens--common principles

Area of Science:

• Immunology
• Rheumatology
• Autoimmunity

Background:

• Antibodies to citrullinated protein (ACPA) are specific serological markers for rheumatoid arthritis (RA).
• RA is not a single entity; ACPA-positive and ACPA-negative RA exhibit distinct characteristics, including genetic predispositions and disease severity.
• A novel autoantibody system targeting carbamylated proteins (anti-CarP antibodies) has been identified in RA patients.

Purpose of the Study:

• To review recent advancements in understanding immune responses against citrullinated and carbamylated proteins in RA.
• To highlight the differences between ACPA-positive and ACPA-negative RA.
• To discuss the role of anti-CarP antibodies in RA pathogenesis.

Main Methods:

• Review of current literature on ACPA and anti-CarP antibodies in RA.
• Analysis of genetic risk factors, disease course, and remission rates in different RA subgroups.
• Discussion of the post-translational modification of lysine to homocitrulline in carbamylation.

Main Results:

• Human leucocyte antigen shared epitope alleles are linked to ACPA-positive RA, not ACPA-negative RA.
• ACPA-positive RA typically presents with a more severe disease course and reduced likelihood of drug-free remission.
• Anti-CarP antibodies recognize carbamylated proteins, where lysine residues are modified to homocitrulline.

Conclusions:

• The identification of ACPA and anti-CarP antibodies has significantly advanced the understanding of RA pathogenesis.
• Distinguishing between ACPA-positive and ACPA-negative RA is crucial for understanding disease heterogeneity.
• Further research into anti-CarP antibodies may reveal new diagnostic and therapeutic strategies for RA.