22 - Science of Rheumatoid Arthritis

Question 1

name 4 changes to a joint which has been affected by RA?

Answer 1

inflamed synovium, inflamed tendon sheath, thinning of joint cartilage and erosion of bone

Question 2

name 4 functions of the synovium?

Answer 2

maintenance of tissue surface, lubrication of cartilage, control synovial fluid volume, nutrition of chondrocytes

Question 3

what 2 substances make up the synovial fluid?

Answer 3

hyaluronan, lubricin

Question 4

define RA?

Answer 4

chronic symmetric polyarticular inflammatory joint disease

Question 5

which joints are usually affected by RA?

Answer 5

small joints of the hands and feet

Question 6

how is rheumatoid synovitis characterised? (3)

Answer 6

inflammatory cell infiltration, synoviocyte proliferation and neoangiogenesis

Question 7

describe the synovial fluid during RA flare?

Answer 7

contains neutrophils

Question 8

what does synovial pannus cause?

Answer 8

bone and cartilage destruction

Question 9

name 2 antibodies commonly associated with seropositive RA?

Answer 9

rheumatoid factors and anti-citrullinated protein antibodies (ACPA)

Question 10

name 1 way in which autoantibodies can contribute to inflammation in RA?

Answer 10

activation of complement

Question 11

how is seropositive RA diagnosed?

Answer 11

anti-CCP assays - these recognise ACPAs

Question 12

name 4 of the ACPAs which may be present in seropositive RA?

Answer 12

alpha-enolase, keratin, fibrinogen, collagen etc.

Question 13

which autoantibodies are associated with seronegative RA?

Answer 13

NONE

Question 14

is there a genetic link with RA?

Answer 14

Yes - esp twins

Question 15

which locus is associated with a risk of developing RA?

Answer 15

HLA-DRB1 locus

Question 16

how does this locus play a role in promoting autoimmunity in RA?

Answer 16

molecular mimicry - these alleles containing common amino acid motif in the HLA-DRB1 region

Question 17

effect of smoking on RA?

Answer 17

increases risk - as well as bronchial stress

Question 18

give an example of 2 infectious agents which may increase risk of RA?

Answer 18

EBV, E. coli

Question 19

what does repeated insults in genetically susceptible individuals lead to?

Answer 19

formation of immune complexes and rheumatoid factor - this altered citrullination of proteins results in ACPA response

Question 20

what is citrullination?

Answer 20

the conversion of arginine into citrulline

Question 21

what enzymes are involved in citrullination?

Answer 21

peptidylarginine deiminases (PADs)

Question 22

name 3 examples of coexisting conditions to RA?

Answer 22

vascular disease, fracture, metabolic syndrome

Question 23

name 4 types of cells which are involved in synovitis in RA?

Answer 23

CD4+ T cells, macrophages, B cells, mononuclear cells

Question 24

name 2 types of stromal cell cytokines which are abundant in RA synovium?

Answer 24

macrophage and fibroblast cytokines

Question 25

what is the role of IL-6?

Answer 25

mediate systemic effects

Question 26

what is the role of neoangiogenesis?

Answer 26

to provide nutrients to hyperplastic synovium

Question 27

how is bone destruction mediated in RA?

Answer 27

by osteoclasts that are activated by RANKL (produced in synovium) and fibroblast-like synoviocytes

Question 28

name 2 genes which are implicated in susceptibility to RA?

Answer 28

class II major histocompatibility complex genes and PTPN22

Question 29

when can increased serum levels of RFs and anti-CCP be seen?

Answer 29

years before onset of arthritis

Question 30

name 2 therapeutic target cytokines?

Answer 30

TNF-alpha and IL-6

Question 31

name 4 systemic effects secondary to uncontrolled inflammation due to RA?

Answer 31

vasculitis, nodules, scleritis, amyloidosis

Question 32

name 5 potential systemic complications of RA?

Answer 32

2y fibromyalgia, anaemia, osteoporosis, fibrosis, 2y Sjorgen's syndrome