RA

Question 1

definition of RA

Answer 1

an illness causes by polyarticular inflammatory arthritis, associated with other systemic symptoms

Question 2

who is most affected by RA?

Answer 2

women

Question 3

requirements for RA diagnosis

Answer 3

patient with at least one joint with DEFINITE clinical synovitis that is not better explained by another disease

(joint distribution, RF/ACPA serology, symptom duration, ESR)

Question 4

common features of joint distribution in RA

Answer 4

carpal, MCP, PIP joints affected. DIP joints spared. subluxation common

Question 5

where does the synovium anchor within the joint?

Answer 5

at the margin of the cartilage and bone

Question 6

early stage RA

Answer 6

inflammation within the joint. synovium thickens by hypertrophy and hyperplasia. joint distention due to inflammatory cells within fluid that is less viscous than normal.

Question 7

middle stage RA

Answer 7

tremendous inflammation of synovium causes bony destruction and cartilage damage at the margin. synovium becomes thickened and looks like wet bread (called pannus).

Question 8

late stage RA

Answer 8

tremendous damage to bone and cartilage. Vascular supply is outstripped by growth of synovium

Question 9

RA vs OA vs Spondylitis

Answer 9

inflammatory disease of synovium affecting small joints of hands/feet
degenerative disease of cartilage affecting hands and weight bearing joints
inflammatory disease of synovium and enthuses, axial and peripheral joints affected

Question 10

shared epitope hypothesis

Answer 10

HLA DR alleles that are associated with RA share an amino acid sequence that constitutes part of antigen binding groove

Question 11

risk factors that might trigger immune response in RA

Answer 11

infectious agent, pesticides, smoking, gingivitis

Question 12

smoking and RA

Answer 12

can cause citrullination in the lungs leading to anti CCP antibodies which direct against residues of type 2 collagen

Question 13

periodontal disease and RA

Answer 13

cause and effect relationship is unclear

Question 14

histology of normal synovium

Answer 14

thin membrane of 1-2 cells deep, supported by fibrous tissue.

Question 15

histology of inflamed RA synovium

Answer 15

thickening of synovial cell layer (hypertrophy), proliferation of the synovium (hyperplasia), perivascular infiltrates of inflammatory cells, increased vascularity

Question 16

how can RA be self perpetuating?

Answer 16

immune cells that infiltrate synovium may organize into germinal centers and perpetuate antigen presentation and autoimmune reaction

Question 17

antibodies indicative of RA

Answer 17

RF and anti-CCP. (can form immune complexes that activate complement and attract other inflammatory cells to synovium)

Question 18

RF (rheumatoid factor)

Answer 18

polyclonal antibody (IgM) that binds to Fc portion of IgG. enhances antigen presenting role of b cells. can self associate into immune complex that fixes complement and activates inflammation.

Question 19

cytokines associated with RA

Answer 19

TNFa, IL6, Lymphotoxin, IFNy

Question 20

what is the boss cytokine in RA?

Answer 20

TNFa

Question 21

mechanism of cartilage destruction in RA?

Answer 21

cytokines activate collagenase/MMPs. when released from fibroblast, works from the outside in. when released from chondrocyte, works from the inside out.

Question 22

mechanism of bone destruction in RA?

Answer 22

cytokines activate RANKL, which is an osteoclast differentiation factor

Question 23

RANK

Answer 23

receptor on pre-osteoclasts and osteoclasts that signals for their differentiation and activation

Question 24

RANKL

Answer 24

membrane bound or secreted protein from stromal cells, osteoblasts, T cells, and synovial fibroblasts that activates RANK

Question 25

OPG (osteoprotegerin)

Answer 25

natural RANK antagonist that is secreted by many different cells, which functions by binding RANKL

Question 26

non joint symptoms of RA patients?

Answer 26

accelerated atherosclerosis (likely due to systemic inflammation), increased risk of infection/malignancy, secondary sjogren’s vasculitis, increased pulmonary autoimmune disease.

Question 27

treatment for RA

Answer 27

inhibit TNFa, inhibit B cell function (rituximab), inhibit co-stimulatory molecules, inhibit cytokine receptors, inhibit RANK activation