Shift in perspective: autoimmunity protecting against rheumatoid arthritis

Area of Science:

• Immunology
• Rheumatology
• Autoimmunity

Background:

• Rheumatoid arthritis (RA) is characterized by autoantibodies like anti-citrullinated protein antibody (ACPA) and rheumatoid factor.
• These autoantibodies are traditionally considered pathogenic, linked to bone erosion, pain, and arthritis in RA.
• Previous research has focused on the detrimental role of autoantibodies in RA pathogenesis.

Purpose of the Study:

• To investigate the pathogenic role of autoantibodies, specifically ACPA, in rheumatoid arthritis.
• To explore the function of B cells in the context of autoimmune responses relevant to RA.
• To identify potential protective mechanisms against experimental arthritis.

Main Methods:

• Cloning and testing of ACPA in mouse models of experimental arthritis.
• Identification and quantification of suppressor B cells in healthy individuals and RA patients.
• Analysis of B cell populations in response to collagen type II.

Main Results:

• Most cloned ACPA demonstrated a protective effect against experimental arthritis in mice.
• Suppressor B cells, selected in response to collagen type II, were identified in healthy individuals.
• A decrease in the numbers of these suppressor B cells was observed in patients with RA.

Conclusions:

• The findings challenge the long-held assumption that ACPA are solely pathogenic in RA.
• Suppressor B cells may play a crucial role in preventing autoimmune diseases like RA.
• Reduced suppressor B cell numbers could contribute to the development of RA and other autoimmune conditions.