This document discusses potential environmental and microbial triggers for the development of rheumatoid arthritis (RA). It notes that smoking can accelerate joint damage in early-stage RA by triggering citrullination of proteins in the lungs. Certain occupations involving noxious airborne agents like construction work also increase RA risk. Microbes in the lungs, mouth, and gut may play a role through citrullination or triggering inflammation, and targeting the microbiome through probiotics or diet could become a therapeutic approach.

1. FA R H A N TA H I R M D
WHERE DOES RA START?

2. SMOKING LINKED TO EROSION
• Strongest environmental exposure
• Triggers citrullination of proteins in the lung
• Citrullination: Amino acids catalyzed to citrulline which is
attacked by the immune system
• In Early-stage RA smoking may accelerates joint
damage
• Erosion Joint Count in smokers vs non smoker averaged
1.2 vs 0.7 (P=0.04)
• No difference in past smokers and nonsmokers
https://www.medpagetoday.com/MeetingCoverage/ACR/29822

3. WORK EXPOSURES LINKED WITH RA
• Sweden: 3,522 cases and 5,580 controls
• Especially in Men, occupations with exposure to noxious
airborne agents at risk
• Bricklayers or concrete workers, material handling
operators, electrical workers odds were almost tripled for
CCP + RA
• For women occupation at risk was assistant nurses and
attendants
• Physical workload may be associated risk
https://www.medpagetoday.com/Rheumatology/Arthritis/67187

4. RA : IMMUNITY, GENETICS, AND
ENVIRONMENT
• Airborne exposures, silica, mineral oil, asbestos,
pesticides, and textile dusts trigger citrullination
• Toxins include organic solvents, metal fragments, and
motor exhaust
• Innate immunity via their effects on toll-like receptors
example is lungs
• Activation of antigen-presenting cells
• Triggering of pro-inflammatory cytokines such as tumor
necrosis factor.
https://www.medpagetoday.com/Rheumatology/Arthritis/67187

5. DOES RA START IN MOUTH?
• 1900s “Oral sepsis" hypothesis led to "therapeutic
edentulation”
• Attention to microbiome and oral cavity as risk
• High frequency and greater severity for periodontal
disease in RA
• P. gingivalis : Peptidylarginine deiminase (PAD) enzyme
citrullinates proteins which trigger autoimmunity
• Antibodies to P. gingivalis in RA
• CCP antibody predate RA
https://www.medpagetoday.com/Rheumatology/Arthritis/45289

6. COULD IT BE THE GUT?
• Gut Bacteria: A Potential Game Changer for Rheumatoid
Arthritis
• NYU researcher studies connection between intestinal
bugs and arthritis
• Prevotella –abundant in people with untreated RA
• May trigger an inflammatory response that targets the
joints

7. NEW FRONTIER
MODIFY THE MICROBIOME
• Interventions targeting the microbiota may become
therapeutically viable for some types of inflammatory
arthritis
• Probiotics, Lactobacillus casei and Lactobacillus
acidophilus, reduced joint inflammation more effectively
than the NSAID indomethacin
• RA Benefit from adopting a Mediterranean diet high in
fish, olive oil and vegetables

8. THANKS
• Contact: irheum@gmail.com
• https://www.linkedin.com/in/irheum
• https://www.irheum.org