RA

Question 1

what is rheumatoid arthritis?

Answer 1

immune-mediated inflammatory disease (autoimmune disease)

Question 2

name the 2 types of synoviocytes in the synovial membrane

Answer 2

type A macrophages
type B fibroblasts

Question 3

what is the function of the synovial membrane?

Answer 3

tight-junction forming resident lining of macrophages form a protective barrier for joint structures, when this disintegrates infiltration of inflammatory myeloid cells occur

Question 4

what is the function of ACPA?

Answer 4

1. induce activation of osteoclasts
2. induce pain behaviour

Question 5

what are osteoclasts?

Answer 5

the precursors that develop into immune cells

Question 6

name the 3 stages of developing seropositive RA

Answer 6

1. risk of developing RA; antibody production
2. ACPA-associated disease; osteoclast activation and IL-8 production
3. ACPA-positive RA; inflammation

Question 7

describe the role of IL-12/Th1 in RA

Answer 7

p40 deficient; no disease
p35 and IFNy deficient; increased disease severity

Question 8

describe the role of IL-23/Th17 in RA

Answer 8

IL-23 is required for the induction of disease, it regulates the inflammatory activity of autoantibodies via altering glycosylation
Th17 produces IL-17A

Question 9

how is early RA diagnosed?

Answer 9

increased CCR6+ memory T cells producing IL-17A and TNFa

Question 10

name 2 treatments for RA

Answer 10

1. targetting IL-17 to neutralize Th17 activity
2. TNF inhibitors

Question 11

how can antibodies contribute to inflammation?

Answer 11

1. by activating complement
2. by binding to Fc-receptors on macrophages (activating and inhibiting)

Question 12

name the 2 autoantibodies in RA

Answer 12

1. rheumatoid factor (RF)
2. antibodies against citrullinated protein antigens (ACPA)

Question 13

name 2 targeted therapies for B cells in RA

Answer 13

rituximab; anti-CD20
tocilizumab; IL6 receptor antagonist

Question 14

what are rheumatoid factors?

Answer 14

1. autoantibodies directed against the Fc-part of IgG
2. IgM, IgG and IgA
3. are able to form large immune complexes
4. role in the clearance of excess of immune complexes after infection

Question 15

what are ACPAs?

Answer 15

general term to all antibodies directed against citrullinated epitopes

Question 16

what are anti-CCP?

Answer 16

cyclic citrullinated peptide; artificial peptide containing citrullinated epitopes

Question 17

what is citrullination?

Answer 17

arginine deimination, post-translational modification of the amino acid arginine into citrulline by peptidylarginine deiminases (PADs)

Question 18

what is the difference between seropositive and seronegative?

Answer 18

seropositive is with autoantibodies and seronegative is without

Question 19

what is fine specificity of ACPA and its hypothesis?

Answer 19

response against specific citrullinated proteins
hypothesis; fine specificity increases in time and after a critical mass has been reached, arthritis occurs

Question 20

what are the 2 hypotheses about the development of RA?

Answer 20

1; ACPA-response does not change, the expression of certain citrullinated epitopes change
2; ACPA-response changes over time, expression of certain epitopes does not

Question 21

what is the 4 roles of B cells in the pathogenesis of RA?

Answer 21

antigen presentation of T cells and antibody production, cytokine production and stimulation via cell-cell interaction

Question 22

Name 2 inflammation markers

Answer 22

CRP and BSE

Question 23

name 2 different DMARDs

Answer 23

1. conventional DMARD; disease modifying anti-rheumatic drug (MTX, SASP, LEF, HCQ)
2. biological DMARD; biological agents that target inflammatory cytokines or cells (monoclonal antibodies, natural antagonists, -mab/cept)