Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start?

Area of Science:

• Immunology
• Rheumatology
• Pathogenesis of Autoimmune Diseases

Background:

• Rheumatoid arthritis (RA) development is preceded by a state of autoimmunity where immune tolerance is broken.
• Seropositive RA is characterized by autoantibodies against post-translationally modified proteins, often induced at extra-articular mucosal sites like the periodontium and lungs.

Purpose of the Study:

• To analyze mechanisms contributing to autoimmunity in at-risk individuals.
• To discuss the relationship between pre-symptomatic autoimmunity and the development of RA.
• To highlight the need for prospective studies defining molecular switches in RA pathogenesis.

Main Methods:

• Review of existing literature on pre-symptomatic autoimmunity in RA.
• Analysis of factors contributing to the transition from at-risk states to systemic autoimmunity and RA.
• Discussion of the potential pathogenic role of autoantibodies and other contributing factors.

Main Results:

• Autoimmunity, marked by specific autoantibodies, precedes clinical RA symptoms in most patients.
• Extra-articular mucosal sites are implicated in the induction of autoantibody responses.
• Factors like gut dysbiosis and dysregulated inflammatory signaling contribute to pre-symptomatic autoimmunity.

Conclusions:

• The transition to RA involves multiple "switches" from at-risk states to systemic autoimmunity and then to clinical disease.
• Further research is needed to elucidate the molecular basis of these switches for targeted preventative strategies.
• Identifying pre-symptomatic autoimmune features is crucial for early intervention in high-risk individuals.