Rheumatoid Arthritis Pathophysiology

Question 1

Signs of RA?

Answer 1

Morning stiffness
Swelling, heat, redness and pain,
Loss of function
Multiple joints in a symmetrical fashion

Question 2

Features of RA?

Answer 2

3x more women than men

Question 3

Prevalence?

Answer 3

Affects 1%

Question 4

Autoantibodies?

Answer 4

Cyclic citrulinated peptide and rheumatoid factor

Question 5

Cytokines in RA?

Answer 5

IL 1/ 6 and TNF alpha
IL6 triggers liver for acute phase response
And stimulates adipocytes leading to diabetes

Question 6

Comorbidities of RA?

Answer 6

MI 
Stroke
Atherogenesis
Low stress tolerance 
Depression 
Fractures

Question 7

Where do the antibodies bind?

Answer 7

Fc portion of igM, igG

Question 8

Autoantibodies are found in how many patients?

Answer 8

60-70%

Question 9

How specific are the antibodies for RA?

Answer 9

86%

Question 10

Patients positive with the antibodies are….?

Answer 10

Have a more severe disease

Question 11

Antibodies against CCp are found in patients percentage?

Answer 11

70-80%

Question 12

Antibodies detect?

Answer 12

Arginine to citrulline change

Fibronectin, collagen

Question 13

Mechanism of anti citrullinated antibodies?

Answer 13

Activation of inflammatory cells by anti CCP immune complexes
Bind to osteoclast
Producing NETs

Question 14

Monozygotic identicals getting RA?

Answer 14

12-15%

Question 15

Dizygotic non-identical chances of getting RA?

Answer 15

2-5%

Question 16

Genes associated?

Answer 16

HLA DRB1 SE- 30-50% of the overall genetic risk
PTPN22- tyrosine phosphatase
CTLA4, downregulated
A20 downregulated, which normally inhibits NF-kB and TNF alpha mediated apoptosis

Question 17

Environmental factors?

Answer 17

Men who have lower testosterone, usually get RA
RA patients often experience remission during pregnancy
Early menopause- RF positive
Oral contraception- decrease of antibodies/ HRT

Question 18

Smoking association?

Answer 18

Increased risk, if you have HLA-DR4

Also smoking with HLA DRB1- increases risk of anti- CCP

Question 19

Periodontitis?

Answer 19

If you have gum disease, more likely to get RA
P gingivalis can citrullinate our proteins, and if you have the HLA DRB1 then you present through ACPs to activated T cells.

Question 20

Synovitis?

Answer 20

Swelling over extensor tendons, wrist and MCP
Synovial hyperplasia ( increase number in cells)
Synovial fibroblasts, sticking to bone and reduced apoptosis

Question 21

What happens in a rheumatoid joint?

Answer 21

Synovial membrane becomes thickened- pan us
Immune cells coming from blood and within the synovial fluid, neutrophils doing NETosis
Thinning of cartilage
Fibroblasts grow into places and infiltrate into the bone

Question 22

Molecular members of inflammation present?

Answer 22

Macrophages 40%

Fibroblasts and endothelial cells 10-15%

Question 23

Pro inflammatory cytokines?

Answer 23

IL 1, 6, 17 and TNF alpha

Question 24

How does cartilage erosion happen?

Answer 24

Chondrocytes undergo apoptosis
Fibroblasts adhere to and invade the cartilage
Fibroblasts make matrix metalloproteases, breaking down the cartilage

Question 25

Osteoclasts are activated by?

Answer 25

RANKL IL17 TNF alpha IL1 and 6

Question 26

In a year how many RA patients develop resorption pits?

Answer 26

80%

Question 27

What do NETs release?

Answer 27

Citrullinated proteins

Question 28

TH 17 cause?

Answer 28

Release IL 17, favour cartilage resorption

And activate synovial fibroblasts and osteoclasts

Question 29

T regulatory cells are not working due to presence of?

Answer 29

TNF

Question 30

Treatment through B cells

Answer 30

Anti CD20

Question 31

Most therapies lead?

Answer 31

Macrophage cytokine production