When and where does rheumatoid arthritis begin?

Area of Science:

• Rheumatology
• Immunology
• Pathophysiology

Background:

• Rheumatoid arthritis (RA) treatments offer symptomatic relief but lack curative potential.
• A deeper understanding of early-stage RA and etiological factors is crucial for developing curative therapies.
• Studies on preclinical RA aim to uncover the disease's origins and progression.

Purpose of the Study:

• To review current literature on preclinical rheumatoid arthritis (RA).
• To identify potential origins and early immunological events in RA development.
• To explore avenues for future preventive strategies against RA.

Main Methods:

• Literature review of studies focusing on preclinical rheumatoid arthritis (RA).
• Analysis of immunological origins and etiological factors in RA.
• Examination of the progression from preclinical phase to clinical arthritis.

Main Results:

• The immunological conflict in RA likely originates outside the joints, possibly in the upper aerodigestive tract.
• The preclinical phase of RA can be prolonged, with some individuals not progressing to arthritis.
• An uncontrolled immunological conflict precedes elevated autoantibody titers and inflammation markers, followed by joint symptoms.

Conclusions:

• Understanding the preclinical phase of RA is key to identifying susceptibility profiles.
• Knowledge of early RA development may enable the future development of preventive strategies.
• Investigating extra-articular origins, such as the upper aerodigestive tract, is vital for RA research.