17b. MSK - RA Flashcards
What is RA?
Chronic, inflammatory AI condition
Synovial joint inflammation
Signs/symptoms of RA
Symmetrical polyarthritis
Affecting small distal joints - hands/feet
Hand deformities
Subcutaneous nodules
Complications of RA
Carpal tunnel syndrome
Sjogren’s syndrome
Kidney disease
C1/2 vertebral subluxation
How does RA start?
Genetics/environmental factors trigger citrullination
(conversion of arginine to citrulline)
What happens after citrullination in RA?
Antigen presenting cells see some parts of the citrulline proteins as foreign
Presents the foreign antigens to CD4 and T cells
Triggers T cell differentiation/B cell activation
Autoantibodies produced
Inflammatory cytokines in synovial joints produced
What do the inflammatory cytokines in the synovial joints stimulate the production of?
Fibroblast-like synoviocytes (FLS) which release proteases
What do the proteases released by the fibroblast-like synoviocytes do?
Cartilage degradation
Increase RANKL expression
What does increased RANKL expression do in RA?
Increases osteoclasts
Increases bone destruction
Causes and risk factors of RA
Genetics
Smoking
P. gingivalis
Infectious agents
Gut dysbiosis
Silica dust exposure
SNPs on which genes are a risk factor for RA?
HLA-DRB1
PTPN22
Why is smoking a risk factor for RA?
Oxidative damage
Raised inflammatory cytokines
Increased MMP expression
Why is P. gingivalis a risk factor for RA?
Produces the PAD enzyme which induces citrullination
Examples of infectious agents that are a risk factor for RA
EBV
Proteus mirabilis
Why is silica dust exposure a risk factor for RA?
Increases inflammatory cytokines
Increases MMP activity
Which bacteria are implicated as risk factors for RA?
Prevotella copri
Collinsella
