The Impact of Rheumatoid Arthritis on First Nations and How We Can Work With Communities to Prevent It

Area of Science:

• Immunology
• Genetics
• Public Health

Background:

• Rheumatoid arthritis (RA) disproportionately affects Indigenous North American First Nations (FN), presenting as severe, familial, and seropositive disease with poor outcomes.
• Genetic predisposition, including specific HLA alleles like *HLA-DRB1*1402*, combined with environmental factors like smoking and periodontal disease, increases RA risk in FN populations.
• Understanding preclinical RA stages is crucial for developing effective prevention strategies in FN communities.

Purpose of the Study:

• To investigate preclinical stages of rheumatoid arthritis (RA) in First Nations (FN) populations.
• To identify anticitrullinated protein antibodies (ACPA) and proteomic biomarkers predicting RA development.
• To evaluate the efficacy of supplements (curcumin, omega-3, vitamin D) for RA prevention in ACPA-positive individuals.

Main Methods:

• Prospective follow-up of first-degree relatives of FN RA patients.
• Screening of FN communities using dried blood spot technology for ACPA detection.
• Enrollment of ACPA-positive individuals in supplement intervention studies (curcumin, omega-3, vitamin D).

Main Results:

• Focus on anticitrullinated protein antibodies (ACPA) and proteomic biomarkers as early predictors of RA.
• Identification of a potential 'point of no return' for irreversible autoimmunity in RA development.
• Exploration of supplement interventions based on preclinical data and mouse models.

Conclusions:

• Gene-environment interactions significantly contribute to RA risk in First Nations populations.
• Early detection of ACPA and biomarkers enables targeted prevention strategies.
• Supplement interventions show promise for preventing RA development prior to irreversible autoimmune processes.